Breast Cancer

CONSENSUS DOCUMENT
FOR MANAGEMENT
OF BREAST CANCER
Prepared as an outcome of ICMR Subcommittee on

Breast Cancer
Indian Council of Medical Research,

Ansari Nagar, New Delhi – 110029
2016
Disclaimer
This consensus document represents the current thinking of experts on the topic based on available
evidence. This has been developed by national experts in the field and does not in any way bind a
clinician to follow this guideline. One can use an alternate mode of therapy based on discussions with
the patient and institution, national or international guidelines. The mention of pharmaceutical drugs for
therapy does not constitute endorsement or recommendation for use but will act only as a guidance for
clinicians in complex decision –making.
Dr. Soumya Swaminathan

Secretary,
Department of Health Research
and Director General, ICMR
Published in 2016
Dr. V. K. Srivastava : Head (Publication & Information)
Compiled & Edited by : Dr. Tanvir Kaur, Scientist ‘F’, Dr. R. Sarin
Production Controller : JN Mathur
Published by the Division of Publication and Information on behalf of the Secretary DHR & DG, ICMR, New Delhi.
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Foreword
I am glad to write this foreword for consensus document for management
of breast cancers. The ICMR had constituted sub-committees to prepare consensus
document for management of various cancer sites. This document is the result of the
hard work of various experts across the country working in the area of oncology.
This consensus document on management of breast cancers summarizes the
modalities of treatment including the site-specific anti-cancer therapies, supportive
and palliative care and molecular markers and research questions. It also interweaves
clinical, biochemical and epidemiological studies.
The various subcommittees constituted under Task Force project on Review
of Cancer Management Guidelines worked tirelessly in formulating site-specific guidelines. Each member
of the subcommittee’s contribution towards drafting of these guidelines deserves appreciation and
acknowledgement for their dedicated research, experience and effort for successful completion. Hope
that this document would provide guidance to practicing doctors and researchers for the management of
patients suffering from breast cancers and also focusing their research efforts in Indian context.
It is understood that this document represents the current thinking of national experts on subject
based on available evidence. Mention of drugs and clinical tests or therapy do not imply endorsement or
recommendation for their use, these are examples to guide clinicians in complex decision making. We are
confident that this first edition of Consensus Document on Management of Breast Cancer would serve
the desired purpose.
Dr. S Swaminathan
Secretary, Department of Health Research
and Director General, ICMR
Message
I take this opportunity to thank Indian Council of Medical Research and all
the expert members of the subcommittees for having faith and considering me as
chairperson of ICMR Task Force project on guidelines for management of cancer.
The Task Force on management of cancers has been constituted to plan
various research projects. Two sub-committees were constituted initially to review
the literature on management practices. Subsequently, it was expanded to include
more sub-committees to review the literature related to guidelines for management
of various sites of cancer. The selected cancer sites are lung, breast, oesophagus,
cervix, uterus, stomach, gall bladder, soft tissue sarcoma and osteo-sarcoma, tongue,
acute myeloid leukemia, acute lymphoblastic leukaemia, CLL, Non Hodgkin’s Lymphoma-high grade,
Non Hodgkin’s Lymphoma-low grade, Hodgkin’s Disease, Multiple Myeloma, Myelodysplastic Syndrome
and Pediatric Lymphoma. All aspects related to management were considered including, specific anti-
cancer treatment, supportive care, palliative care, molecular markers, epidemiological and clinical aspects.
The published literature till October 2015 was reviewed while formulating consensus document and
accordingly recommendations are made.
Now, that I have spent over a quarter of a century devoting my career to the fight against cancer,
I have witnessed how this disease drastically alters the lives of patients and their families. The theme
behind designing of the consensus document for management of cancers associated with various sites
of body is to encourage all the eminent scientists and clinicians to actively participate in the diagnosis
and treatment of cancers and provide educational information and support services to the patients
and researchers. The assessment of the public-health importance of the disease has been hampered
by the lack of common methods to investigate the overall worldwide burden. ICMR’s National Cancer
Registry Programme (NCRP) routinely collects data on cancer incidence, mortality and morbidity in India
through its co-ordinating activities across the country since 1982 by Population Based and Hospital
Based Cancer Registries and witnessed the rise in cancer cases. Based upon NCRP’s three year report
of PBCR’s (2012-2014) and time trends on Cancer Incidence rates report, the burden of cancer in the
country has increased many fold.
In summary, the Consensus Document for management of various cancer sites integrates
diagnostic and prognostic criteria with supportive and palliative care that serve our three part mission
of clinical service, education and research. Widespread use of the consensus documents will further help
us to improve the document in future and thus overall optimizing the outcome of patients. I thank all the
eminent faculties and scientists for the excellent work and urge all the practicing oncologists to use the
document and give us valuable inputs.
(Dr. G.K. Rath)

Chairperson
ICMR Task Force Project
Preface
With urbanization and changes in life style, there is increasing incidence
of carcinoma of the breast and it is estimated that every year 144,000 women are
diagnosed with breast cancer. The incidence of breast cancer is higher in urban
India, especially the metropolitan cities where it is now the leading female cancer
and is the second most common cancer after cervix in rural and semi-urban India.
As for other cancers in India, late stage presentation is also a common scenario for
breast cancer.
Breast cancer being the most common female cancer in the west, has
been the subject of a large number of biological, pathology and therapeutic studies
including numerous randomized trials and meta-analysis, examining in detail almost all aspects of disease
management. However as most breast cancer patients in the west are now diagnosed with early stage or
screen detected cancers, relatively fewer modern studies have focused on locally advanced breast cancer
(LABC). While there is level I evidence for the safety and efficacy of breast conservative treatment (BCT)
for operable breast cancer, high quality evidence does not exist for this approach in LABC. While there
is a general consensus regarding the use of neo-adjuvant or adjuvant chemotherapy in locally advanced or
node positive breast cancer, there is lack of consensus among Indian oncologists for its use in small node
negative cancers. We still have wide discrepancy across the country in terms of the availability and the
quality of breast imaging; breast pathology including IHC and FISH; breast conserving surgery and axillary
surgery; Linac based and cardiac sparing RT; and supportive care for complications of chemotherapy. As
a result all eligible women are not offered BCT, many centres routinely give axillary RT in node positive
cancers due to inadequate axillary surgery or its pathology reporting; radiotherapy (RT) practices are not
standardized; and maintaining dose intensity and optimal scheduling of chemotherapy with surgery and RT
and timely management of acute toxicity remains challenging. Only a fraction of women with breast cancer
in India receive comprehensive multimodality treatment under one roof and under the expert guidance of a
multidisciplinary team. Hence it is not always possible to directly apply some of the treatment approaches
for which the trials in the west have shown clinical benefit. A panel of experts which included Radiation,
Surgical and Medical oncologists, radiologists, pathologists and palliative care specialists have drafted this
consensus and its applicability in the Indian setting. There is a need to have multi-disciplinary teams for
evidence based management for all breast cancer patients. Provision of palliative care and availability of
morphine is also an integral part of managing metastatic cancer.
The document has been designed to optimize the outcome of the patients based on the available
evidence as well as the resources at majority of the regional cancer centers. This will bring uniformity in
the practice of this disease at various cancer treatment centers and thus promote seamless collaborative
studies to address India specific research questions.
(Dr. R. Sarin)
Chairperson,
Subcommittee on breast Cancer
Preface
Cancer is a leading cause of death worldwide. Globally Cancer of various types
effect millions of population and leads to loss of lives. According to the available data
through our comprehensive nationwide registries on cancer incidence, prevalence
and mortality in India among males cancers of lung, mouth, oesophagus and
stomach are leading sites of cancer and among females cancer of breast, cervix are
leading sites. Literature on management and treatment of various cancers in west
is widely available but data in Indian context is sparse. Cancer of gallbladder and
oesophagus followed by cancer of breast marks as leading site in North-Eastern
states. Therefore, cancer research and management practices become one of the
crucial tasks of importance for effective management and clinical care for patient in
any country. Hence, the need to develop a nationwide consensus for clinical management and treatment
for various cancers was felt.
The consensus document is based on review of available evidence about effective management and
treatment of cancers in Indian setting by an expert multidisciplinary team of oncologists whose endless
efforts, comments, reviews and discussions helped in shaping this document to its current form. This
document also represents as first leading step towards development of guidelines for various other cancer
specific sites in future ahead. Development of these guidelines will ensure significant contribution in
successful management and treatment of cancer and best care made available to patients.
I hope this document would help practicing doctors, clinicians, researchers and patients in complex
decision making process in management of the disease. However, constant revision of the document
forms another crucial task in future. With this, I would like to acknowledge the valuable contributions of all
members of the Expert Committee in formulating, drafting and finalizing these national comprehensive
guidelines which would bring uniformity in management and treatment of disease across the length and
breadth of our country.
(Dr. R.S. Dhaliwal)

Head, NCD Division
Acknowledgement
The Consensus Document on Management of Cancer is a concerted outcome of
effort made by experts of varied disciplines of oncology across the nation. The
Indian Council of Medical Research has constituted various sub committees to
formulate the document for management of different cancer sites. The Task Force
on Management of Cancers has been constituted to formulate the guidelines for
management of cancer sites. The sub-committees were constituted to review to
review the literature related to management and treatment practices being adopted
nationally and internationally of different cancer sites. The selected cancer sites are
that of lung, breast, oesophagus, cervix, uterus, stomach, gallbladder, soft tissue
sarcoma and osteo-sarcoma, tongue, acute myeloid leukaemia, ALL, CLL, NHL-high grade, NHL-low
grade, HD, MM, MDS, and paediatric lymphoma. All aspects related to treatment were considered including,
specific anti-cancer treatment, supportive care, palliative care, molecular markers, epidemiological and
clinical aspects.
This document represents a joint effort of large effort of large number of individuals and it is my pleasure
to acknowledge the dedication and determination of each member who worked tirelessly in completion
of the document.
I would like to take this opportunity to thank Dr. GK Rath, chairperson, ICMR Task Force on Guidelines
for Management of Cancer for his constant guidance and review in drafting the consensus document.
The chairperson of subcommittee. Dr Rajiv Sarin, is specially acknowledged in getting the members
together, organizing the meetings and drafting the document.
I would like to express gratitude to Dr. Soumya Swaminathan, Secretary, Department of Health Research
and Director General, Indian Council of Medical Research, for taking his special interest and understanding
the need of formulating the guidelines which are expected to benefits the cancer patients.
I would like to acknowledge here the initiative undertaken with the able guidance of Dr. Bela Shah.
I would like to thank Dr. R.S. Dhaliwal for his support and coordination in finalizing this document. I
would like to acknowledge the assistance provided by administrative staff. This document is the result
of the deliberations by subcommittees constituted for this purpose. The guidelines were further ratified
by circulation to extended group of researchers and practitioners drawn from all over the country. It is
hoped that these guidelines will help the practicing doctors to treat cancer patients effectively and thus
help them to lead a normal and healthy life.
The ICMR appreciatively acknowledges the valuable contribution of the members for extending their
support in formulating these guidelines. The data inputs provided by National Cancer Registry Programme
are gratefully acknowledged.
(Dr.Tanvir Kaur)
Programme Officer & Coordinator
Members of the Sub-Committee
Chairperson
Dr.R.Sarin
Prof. Radiation Oncology & I/C Cancer Genetics Unit
Tata Memorial Hospital,
Mumbai
Members
Dr.G.K.Rath Dr Vani Parmar
Chief Professor, Surgical Oncology & Convener
IRCH Breast Disease Management Group
All India Institute of Medical Sciences Tata Memorial Hospital, Mumbai
New Delhi
Dr. Sudeep Gupta
Dr.Sandeep Kumar Professor of Medical Oncology
Director Tata Memorial Hospital
All India Institute of Medical Sciences Mumbai
Bhopal
Dr.S.Thulkar
Dr.R.Nimmagada Professor of Radiology
Senior Consultant IRCH, All India Institute of Medical Sciences
Department of Medical Oncology, New Delhi
Apollo Hospital,
Chennai Dr. M. Muckaden
Professor,
Dr Prabha Yadav Department of Palliative Care,
Professor Tata Memorial Hospital, Mumbai
Department of Plastic &
Reconstructive Surgery,
Mumbai
Dr. T. Shet
Professor,
Department of Pathology,
Mumbai
table of Contents
Foreword i
Message from Chairperson ii
Preface (Chairperson of Subcommittee) iii
Preface iv
Acknowledgement v
1. Breast Cancer in India and need for Management Guidelines 11
2. Breast Cancer Epidemiology and Screening 13
3. Breast Cancer Staging & Prognostic criteria 14
4. Diagnostic Evaluation and Staging Work up 16
5. Management of Breast Cancer 19
6. Surgery for Breast Cancer 23
7. Histopathological Evaluation and Reporting 24
8. Systemic Therapy 27
9. Radiotherapy 29
10. Follow up 31
11. Metastatic breast cancer 32
12. Hereditary Breast Cancer 35
13. Research Issues 37
14. Bibliography 38
1
CHAPTER
BREAST CANCER IN INDIA AND NEED FOR MANAGEMENT

GUIDELINES
B
reast cancer is the most common female cancer in the world with an estimated 1.67 million new
cancer cases diagnosed in 2012. While the age adjusted incidence rates of breast cancer in India
is lower than the western countries, because of the large population the burden of breast cancer
is high. With an annual incidence of approximately 1,44,000 new cases of breast cancers in India, it has
now become the most common female cancer in urban India1.
There is general consensus in Indian oncologists regarding the use of surgery, with breast conservation
when feasible and the indication for radiotherapy, chemotherapy and hormone therapy in various stages
of breast cancer. Breast conservation rates are low even for stage I & II breast cancers in most Indian
centres and reflects the lack of access to modern radiotherapy. The quality of mastectomy, axillary
lymph node dissection and pathology reporting varies significantly across the country. The choice of
chemotherapy regimen and hormonal agents for different stages of breast cancer is determined not only
by the prognostic and predictive factors but also by the logistics and access. Similarly the treatment for
recurrent or metastatic disease is not uniform and is governed by several factors including the previous
treatment, patient’s ability to tolerate additional treatment and access to such treatment. For Indian
women with operable breast cancer who received standard multimodal treatment in the control arm of a
recently published large randomized clinical trial from Tata Memorial Hospital (TMH), the 5 year disease
free survival (DFS) rate of 70% and overall survival rate of 78% was reported2.
In resource constrained countries with low per capita income, high out of pocket expenses on health care
and long waiting lists in publically funded institutes, threshold for adopting a diagnostic or therapeutic
approach in routine practice requires careful consideration of the strength of evidence for long term clinical
benefit, resource implications and cost effectiveness. Safe and effective strategies should be developed,
standardized and propagated taking in account the feasibility of safely executing them in majority of
departments across the country. Despite major advances in terms of availability of modern technology
in India and expertise to use it in the last decade, a significant proportion of cancer patients either do
not have access to or cannot afford state-of-the-art treatment. Hence there is a need to define the scope
and limitations of approaches that would be more accessable or affordable and what would be considered
ideal in western countries.
Several international and national consensus guidelines from professional bodies and expert panels
are available for the management of breast cancers. The widely used international guidelines are from
the National Comprehensive Cancer Network (NCCN)3, St.Gallen International Expert Consensus4 and
the European Society of Medical Oncology (ESMO)5-7 and the National Institute for Health and Care
Excellence (NICE) of the U.K8. These are based on evidence from clinical trials from a patient population
which in general has better tolerance to systemic chemotherapy and greater access of high quality care
required for optimal management of acute and late complications of treatment. Therefore, it is important
11 Consensus Document for Management of Breast Cancer

to formulate guidelines which takes in to account not only the robust scientific evidence generated
through large randomized trials in the western population but also the feasibility of implementing them
in routine clinical practice, differences in patients tolerance and wherever it is available, the Indian data
and experience. Few Indian guidelines and expert consensus statements covering major aspects of breast
cancer management are also published9,10.
Considering that there are very few large randomized trials or prospective studies from India and there
are notable differences in the age and disease stage at presentation one has to exercise caution in directly
extrapolating results of RCTs conducted in the west to our population. Providing treating doctors with
uniform guidelines for the management of Breast cancer appears to be an appropriate step forward in
achieving this goal.The following chapters review the existing National and International guidelines for
breast cancer and their applicability in the Indian context.

2
CHAPTER
BREAST CANCER EPIDEMIOLOGY AND SCREENING
I
n India the incidence of breast cancer is significantly lower than western countries. Breast cancer in
India varies from as low as 5 per 100,000 female population per year in rural areas to 30 per 100,000
female population per year in urban areas11. There is an impression of higher incidence of breast cancer
in younger women in India as most hospital based series report median age of breast cancer patients
a decade younger than western series. However this may be due to a combination of the population
structure and inherent bias against referral, treatment and ascertainment of breast cancer in the elderly
in India rather than a true reflection. The incidence of breast cancer increases with age and this is true
in India like rest of the world. With the exception of 5-10% breast cancers where the main risk factor is
genetic predisposition, in the remaining 90% of sporadic breast cancers, the identified risk factors are
either reproductive, lifestyle or environmental factors, primarily through their influence on the hormonal
milieu. No breast cancer risk factor, unique to the Indian population has been widely reported.
Breast cancer screening using various approaches has been the subject of several large randomized trials in
USA, Canada and Europe. Population-based mammographic screening of asymptomatic postmenopausal
women has shown a modest reduction in breast cancer deaths in high incidence affluent western countries
but with associated over diagnosis and overtreatment12.
However population-wide mammographic screening program of asymptomatic women is neither feasible
in India nor it may be as useful due to lower breast cancer incidence and population structure in India13.
Opportunistic screening may be considered for some high risk and concerned women in India.
Periodic physical examination of breast by trained health workers along with health education is being
compared with only health education in an ongoing NIH sponsored randomized trial in Mumbai14.
Breast Self Examination (BSE) by women may help in identifying breast tumors earlier but there was no
reduction in breast cancer mortality in one randomized screening trial of BSE versus no intervention15.

3
CHAPTER
STAGING AND PROGNOSTIC CRITERIA
B
reast cancer staging is done after careful clinical evaluation and appropriate investigations as
described in the next chapter. The staging system has evolved over the decades from simple
classification of breast cancer as operable, inoperable to metastatic cancer to more detailed UICC
and AJCC TNM system. The two commonly used staging system are outlined here.
PRAGMATIC CLINICAL STAGING SYSTEM
A) Operable Breast Cancer (OBC): T1-2, N0-1,M0
T1-2: Primary Tumor size up to 5 cm without skin or chest wall involvement
N0-1: Clinically uninvolved axilla or mobile axillary nodes
M0: No metastatic disease on relevant investigative work up
B) Large Operable Breast Cancer (LOBC): T3, N0-1,M0
T3: Primary tumour size >5 cm without skin or chest wall involvement
N0-1: Clinically uninvolved axilla or mobile axillary nodes
C) Locally Advanced Breast Cancer (LABC): T4 or N2-3,M0
T4: Primary Tumor of any size but involves skin or chest wall
N2-3: Matted or fixed axillary nodes or supraclavicular or internal mammary nodes
D) Metastatic Breast Cancer (MBC): Any T or N stage with distant metastasis (M1)
TNM STAGING SYSTEM (Clinical)

Primary tumour
Tx Primary tumour cannot be assessed
Tis In Situ carcinoma
T1 Primary Tumor size up to 2 cm without skin or chest wall involvement
T2 Primary Tumor size up to >2 cm up to 5 cm without skin or chest wall involvement
T3 Primary tumour size >5 cm without skin or chest wall involvement
T4 Primary tumour involves skin, chest wall, satellite nodules or inflammatory breast cancer
T4a Involves chest wall
T4b Involves skin
T4c Involves skin and chest wall
T4d Inflammatory breast cancer
Lymph nodes
Nx Nodes cannot be assessed
No Clinically uninvolved axilla
N1 Mobile ipsilateral level I or II axillary nodes

N2a Matted or fixed ipsilateral axillary nodes
N2b Ipsilateral Internal Mammary Nodes (IMN) without axillary nodes
N3a Ipsilateral Infraclavicular lymph nodes
N3b Ipsilateral IMN + axillary nodes
N3c Ipsilateral Supraclavicular nodes
Metastasis
M0 No metastatic disease on relevant investigative work up
M1 Metastatic disease
TNM STAGING SYSTEM (Pathological)

Primary tumour
pTx Primary tumour cannot be assessed
pTis In Situ carcinoma
pT1 Primary Tumor size up to 2 cm without skin or chest wall involvement
pT2 Primary Tumor size up to >2 cm up to 5 cm without skin or chest wall involvement
pT3 Primary tumour size >5 cm without skin or chest wall involvement
pT4 Primary tumour involves skin, chest wall, satellite nodules or inflammatory breast cancer
pT4a Involves chest wall
pT4b Involves skin
pT4c Involves skin and chest wall
pT4d Inflammatory breast cancer
pNx Nodes cannot be assessed
Lymph nodes
pNo No regional lymph node metastasis identified histologically
pN1mi Micro-metastasis (> 0.2 mm but < 2.0 mm)
pN1a 1-3 axillary nodes
pN1b Ipsilateral Internal Mammary Nodes (IMN) on sentinel node biopsy without axillary nodes
pN1c N1a + N1b
pN2a 4-9 axillary nodes
pN2b Clinically apparent IMN without axillary node metastasis
pN3a ≥ 10 axillary LNs OR Infraclavicular LNs involved.
pN3b Clinically apparent IMNs + positive axillary nodes OR >3 axillary nodes + IMN only on SLN biopsy
pN3c Ipsilateral supraclavicular lymph nodes
Metastasis
M0 No metastatic disease on relevant investigative work up
M1 Metastatic disease

4
CHAPTER
DIAGNOSTIC EVALUATION AND STAGING WORK UP
B
reast cancer is prone to systemic spread, the probability of which increases with tumour size, local
infiltration and lymph node metastasis. Some investigations are essential for clinical management,
especially if the desirable investigations are not feasible due to various reasons and indicated
against each investigation for different stages of the disease.
OBC LOBC/LABC MBC Purpose/ Comments
RoutineTests YES YES YES To assess fitness for anesthesia & chemotherapy
(CBC, Biochemistry)
Breast Imaging YES YES *In selected B/LMammography: If the breast lump is
(see flow chart) cases where suspected to be malignant, especially if BCT is
it is clinically being considered.
indicated USG: If cystic/ benign lesion is suspected,
especially in young women
MRI: In expert centres breast MRI is useful
in screening or characterizing breast lump if
mammography is sub-optimal due to dense
breast (as in some young women) or prior breast
reconstruction. Specially useful for screening
young women at high risk of developing breast
cancer due to family history or BRCA mutation
Cytological/ YES YES YES Core biopsy: Preferred method in all cases and
Histopathological mandatory if Neo- adjuvant systemic therapy is
Confirmation of planned for histological grading and receptor
diagnosis status. To mark the site of the primary tumor the
core biopsy should be centered over the tumor.
FNAC: is acceptable in cases with clinical and
mammographically evident cancer planned for
upfront surgery.
Incision or Excision Biopsy: When there is high
clinical suspicion and repeated FNAC/core biopsy
are negative
ER/ PR YES YES YES IHC (>1% tumour cells staining for ER considered
ER+ve)16.
HER2 #YES #YES #YES #More relevant in cases for whom Traztuzamab
is feasible Standardized IHC for HER2; If IHC is
equivocal (2+) then FISH
ChestX Ray YES YES YES To assess fitness for anesthesia and for staging in
LOBC / LABC
BoneScan
17
*No ^YES ^YES *If raised Alkaline Phosphatase or bone
symptoms/sign
^If Bone scan not feasible due to various logistical
or healthcare provision issues, perform Skeletal
survey, especially if symptomatic.

17USGAbdomen *No ^YES ^YES *If abnormal LFT or suspicious symptoms / signs.
^Not required if CT Thorax & Abdomen is being
performed
17CTThorax *No ^YES ^YES *If abnormal LFT or suspicious symptoms / signs.
/Abdomen ^If CT Scan is not feasible due to various logistical
or healthcare provision issues, Chest X Ray and
USG Abdomen for staging
FDG PET/CT Scan No #In selected cases #In selected #Specially useful if standard imaging findings are
cases equivocal.
Tumour markers No No No Clinical Utility in making diagnosis and disease
(CA-15.3 etc) monitoring not yet established
Multi-gene *No Notapplicable Not Their clinical utility and added value in routine
Signature applicable practice is as yet unknown and there is very little
Mammaprint and data in the Indian patients. Recently an IHC4 test
Oncotype Dx (ER,PR, HER2 and Ki-67) seems to provide useful
information and is advocated by NICE in research
settings
Partly adapted from NCCN/ ESMO/ NICE practice guidelines)4-9

4.1 EVALUATION OF A BREAST LUMP
All women with a breast lump should undergo a TRIPLE TEST comprising of
1. Clinical Examination by experienced clinician, preferably a breast surgeon.
2. Breast Imaging#: Bilateral Mammogram and or Ultrasound or MRI as appropriate.
3. Histopathology*: FNAC / Core biopsy (Ideal). Excision Biopsy/Incision biopsy if indicated.
Based on clinical examination and appropriate breast imaging the lump can be classified as cystic or solid.
Based on the index of suspicion for malignancy (age, clinical finding, family history or previous breast
biopsy findings) solid lesions can be further characterized as likely benign or suspicious for cancer. This
will be the basis of their further evaluation as described below:
A) CYSTIC18,19: Breast Ultrasound followed by clinically guided or USG guided cyst aspiration. Women
with small multiple cysts or if there is clear fluid on aspiration can be observed. Cytology / histopathology
evaluation* is advised for cysts which are complex or hemorrhagic, refill rapidly or have a residual
lump.
B) SOLID BENIGN: Should be evaluated with breast imaging# and excision biopsy if solid
C) SUSPICIOUS SOLID: Should be evaluated with breast imaging# and if on imaging the lump is still
suspicious it should be evaluated with cytology / histopathology*
BENIGN: Excision biopsy
MALIGNANT: Follow relevant algorithm
# IMAGING MODALITY FOR BREAST LESIONS
1. If clinically it is a cyst: evaluate by USG.
2. If less than 30yrs and clinically benign: evaluate by USG.
3. If above 30 yrs or below 30 yrs with clinical suspicion: evaluate by Mammography+/-USG.

4. While there is no defined role of routine breast MRI prior to Breast Conserving surgery20, in centres
with experience in Breast MRI, it may be used in women with
a. Premenopausal women with dense breasts & equivocal mammogram if BCT is planned.
b. Screening high risk women due to family history or BRCA mutation8.
c. Axillary node metastasis without clinical/mammographic evidence of breast primary.
d. Optimal mammographic evaluation is not possible due to breast reconstruction or implants.
*HISTOPATHOLOGY CONFIRMATION:
1. Core biopsy is preferred for all cases, especially if Neoadjuvant chemotherapy is planned (for grading
and receptor status) and for guided biopsy of non-palpable lesion. Biopsy to be centered over the
tumor to mark it location.
2. In our country with infrastructure issues, FNAC is acceptable provided multiple passes are done &
quality smears are prepared. On site evaluation with rapid Diff Quick Stain ensures reducing number
of non diagnostic FNAC’s.
3. For papillary tumors and intraductal carcinoma, excision biopsy for definite diagnosis.
4. Incision/Excision Biopsy: If high clinical suspicion and repeated FNAC or core biopsies are negative.
5. Frozen section is useful in expert centres if all above fail. Not recommended for papillary lesions &
complex sclerosing lesions.
4.2 EVALUATION FOR NIPPLE DISCHARGE
Based on detailed history and clinical examination, in women without any associated breast lump or
abnormal mammogram, further evaluation is based on the colour of the nipple discharge as described
below:
A) Galactorrhoea/White:
If the woman is not lactating or pregnant then serum prolactin and thyroid profile should be done and
reassessed
B) Grumous/Greenish:
Consider a course of antibiotics if the nipple discharge is not blood stained and negative for RBC, especially
if it is associated with inflammation. Should be reassessed.
C) Serous/Yellow/Blood-stained:
Perform breast imaging with mammography and or USG
1. Single duct involved: For spontaneous, profuse, blood stained discharge or presence of RBC on
cytology, consider excision of the duct (Microdochectomy)
2. Multiple ducts involved: For profuse multiple duct involvement especially in postmenopausal women,
consider Hadfield’s surgery.

5
CHAPTER
MANAGEMENT OF BREAST CANCER
Management of breast cancer depends on several patient related factors, disease stage and predictive and
prognostic factors as outlined below
1. Age
2. Menopausal status
3. Family history of cancer
4. Comorbidities especially pre-existing cardiac conditions and long standing poorly controlled
hypertension, diabetes or obesity
5. Performance status and adequate renal and liver function
6. Tumor size and infiltration of skin or chest wall
7. Involvement of nipple with Paget’s disease or nipple discharge
8. Radiological characteristics of the primary tumour – especially the nature and extent of micro-
calcification
9. Site and extent of nodal metastasis
10. Distant metastasis if any, its site (bone only or visceral) and extent
11. Histological features like grade, lymphatic invasion, resection margins and EIC
12. Estrogen or Progesterone receptor status of primary or recurrent tumour or metastatic sites
13. HER-2 expression in primary or recurrent tumor or metastatic sites
14. Proliferative markers and gene signature in some cases
15. Psycho-social and body image issues
16. Patients wishes
17. Patients likely compliance with full treatment and follow up
18. Access to health care, family and social support and affordability
5.1 Management Algorithm for DCIS and DCIS with Micro-invasion
Ductal Carcinoma In Situ (DCIS) is being increasingly diagnosed in the west due to widespread use of
screening mammography. The natural history of screen detected DCIS is variable and many of these will
not progress and may have remained clinically silent during the women’s lifetime.
Imaging for DCIS is similar to breast cancer and takes in to account the patient’s age, breast density and
whether breast conservation is planned or not.
Core Biopsy is necessary for histopathological confirmation. For impalpable lesions it should be image
guided biopsy and performed in centres with experience.

Surgery followed by tamoxifen is the mainstay of treatment. Post-operative RT is required after BCT in
women at higher risk of recurrence as described below.
Lumpectomy21,22 with Axillary Sampling or Sentinel Node Biopsy23 is considered for DCIS without diffuse
micro-calcification or multicentric disease.
Simple mastectomy21 with or without reconstruction is performed for large or multicentric DCIS or when
there is diffuse micro-calcification.
Adjuvant treatment with Tamoxifen (for ER/PR +ve tumors) or Radiotherapy after lumpectomy reduces
the risk of local recurrence of DCIS and invasive cancer24-26. Tamoxifen also reduces risk of contralateral
DCIS and cancer.
Use of adjuvant Tamoxifen and Radiotherapy (after lumpectomy) is guided by the University of Southern California
/ Van Nuys Prognostic index (USC/VNPI). This stratifies a patient into high (10-12), intermediate (7-9) or
low risk (4-6) based on the criteria which individually scores as 1, 2 or 3 as described below:
•• Age (>60, 40-60, <40)
•• Tumor grade & comedo necrosis (low grade, high grade without comedo necrosis, high grade with
comedo necrosis)
•• Tumor size (<1.5cm, 1.6-4cm, >4.1 cm)
•• Margin from resection (>10mm, 1-9mm, <1mm)
Palpable DCIS with or without micro-invasion is the most common presentation of DCIS in India. In such
scenario, role of adjuvant chemotherapy should be carefully considered especially in HER2/neu +ve and
ER/PR –ve DCIS or micro-invasive tumors27.
5.2 Management Schema in Operable Breast Cancer (T1-2, N0-1, M0)
Clinical Diagnosis of Operable Breast Cancer
Histopathological confirmation and Breast Imaging as describe earlier
Wishes for & *Eligible for BCT Want BCT but presently NOT suitable Not wanting OR Not eligible
(>4 cm tumour in small breast) Multicentric tumour or
diffuse micro-calcification
Neo-Adjuvant Chemotherapy
Reassess after 4-6 cycles for BCT
BCT followed by MRM Followed by

Adjuvant therapy Adjuvant Therapy
Neo-Adjuvant & Adjuvant Systemic Therapy (Chemotherapy, Hormone Therapy and Biological agents):
Individualized as per the disease stage, menopausal status, receptor status, other prognostic or predictive
factors along with the tolerance, compliance, feasibility and cost-benefit aspects of a particular approach.
Indication, regimes and sequencing are described later in this document.
Adjuvant Radiotherapy: Post Operative radiotherapy (usually after completion of chemotherapy) is indicated
in all patients undergoing BCT and after mastectomy if T3 or +ve resection margins or >3nodes. For

1-3 +ve nodes, it is being increasingly considered as discussed later. Accelerated Partial Breast Irradiation
(APBI) with various techniques is an option for highly select cases in experienced centres. RT indications
and dose regimes are described later.
*Eligibility for BCT: The breast conservation approach would be considered successful if it produces
satisfactory cosmetic outcome and the probability of tumor control or late sequelae are not inferior to
mastectomy. This requires careful evaluation and selection of cases; good quality breast imaging; wide
excision of primary with appropriate axillary surgery by experienced surgeons; meticulous histopathological
evaluation and reporting of resected specimen; quality assured technique of radiotherapy delivery to
standard doses and regular clinical and mammographic follow up to detect and salvage breast recurrences
early. This would require infrastructure, equipment (e.g. LINAC which is required in >75% BCT cases) and
expertise. Centres with requisite facilities and expertise (sometimes shared between the referring and the
referral centre) should offer BCT to eligible women or if they lack such facilities refer the eligible women
who wish to conserve their Breasts to such centres.
Absolute contra-Indication: Diffuse micro-calcification; multicentric tumor involving >1 quadrant; resection
margins +ve on repeated excisions and EIC+; serious concerns over patient’s likely compliance with RT
and follow up; rare syndromes of radiation hypersensitivity; previous chest/ breast RT.
Relative contra-indication: If lump to breast size ratio precludes acceptable cosmesis even after NACT,
BCT with acceptable cosmetic outcome can be obtained with reconstruction or oncoplasty in expert
centres.
5.3 Management Schema in Large Operable or Locally Advanced Breast Cancer
Clinical Diagnosis of Large operable (T3, N0-1) or Locally Advanced (T3-4 any N; N2-3 any T) Breast Cancer
Hispathological confirmation and Breast Imaging as described earlier
Metastatic-work-up as described earlier
No metastatic disease Metastatic Disease
Mastectomy with Primary skin closure Follow relevant algorithm

for Metalistic Breast Cancer
Feasible Not Feasible
MRM Patient keen Neo-Adjuvant

followed for BCT Chemotherapy (NACT)
by
adjuvant
therapy Assess response after 4 cycles of chemotherapy
In responding patients, Complete all No Response

NACT cycles before Surgery OR
Perform Surgery after 3-4 cycles &
than give remaining chemotherapy
MRM (standard)/BCT (optional)1,2 Mastectomy OR

2nd line chemo
(Based on operability)
Completion of Chemotherapy and Adjuvant

Hormone therapy and Radiotherapy

Systemic Therapy: Chemotherapy, Hormone Therapy or Biological agents are individualized as per the
disease stage, menopausal status, ER/ PR/Her2, other prognostic or predictive factors along with the
tolerance, compliance, feasibility and cost-benefit aspects of a particular approach as described later.
Adjuvant Radiotherapy: Post Operative radiotherapy, usually after completion of chemotherapy to all
LOBC /LABC patients irrespective of the type of surgery. Radiotherapy regimes described later.
Ref: 1. Parmar V et al(2006 ) Int J Surg 4:106–114. 2. Mamounas EP et al.ASCO Breast Symp 2010. Abstract 90
5.4 Management Schema for patients presenting after lumpectomy / excision elsewhere with or without
sufficient clinico-pathological information (a common presentation)
•• Detailed history for the site and size of primary and features suggestive of skin involvement.
•• Clinical examination for breast scar, indurations, residual lump, skin, nodal and distant sites.
•• Review pre biopsy breast imaging films & reports if available and repeat if feasible
•• Review pathology report and blocks, if available, for tumor size, margins, type, grade, ER/PR
•• Metastatic-work-up if features of LOBC/ LABC cannot be ruled out.
Review T size, margins & other Clinical / Imaging features for likely pre-op status (OBC/LOBC/LABC)
Wishes for & eligible for BCT Not wanting OR not eligible for BCT Want BCT but presently NOT suitable
(e.g. Multicentric tumour or (margin +ve or unknown & post Biopsy
diffuse micro-calcification) induration precludes cosmetically
acceptable re-excision)
Wide excision Inadequate MRM

has been done. excision. Margins followed by
Margins free +ve or unknown adjuvant therapy
Only If feasible, Revision excision with

Axillary Revision excision + acceptable cosmesis not
dissection Axillary dissection feasible due to post
biopsy Tumour Bed
induration/skin changes
Neo-Adjuvant Chemotherapy
Adjuvant therapy (Chemo / Hormone /
After 3-6 cycles when induration / skin changes
RT) as per pathological stage & features
resolve, consider Revision Excision + Ax. Dissection
in cases suitable for BCT or MRM
Systemic Therapy: Use of chemotherapy, hormone therapy and biological agents is individualized as per
the disease stage, menopausal status, receptor status, other prognostic/ predictive factors & the tolerance
/compliance/feasibility/cost-benefit aspects of a particular approach. Indication, regimes and sequencing
described later in this document.
Adjuvant Radiotherapy: Post Operative radiotherapy, usually after completion of chemotherapy to all
women undergoing BCT and all women undergoing mastectomy if LOBC /LABC cannot be reliably
ruled out. Radiotherapy fields and dose regimes are described later.

6
CHAPTER
SURGERY FOR BREAST CANCER
T
he indications for BCT or mastectomy and its sequencing with chemotherapy are described in
the previous chapter on management algorithms. Indications for special surgical procedures are
described here.
Sentinel node biopsy and Axillary sampling: Several RCTs 28,29 show that in women with small tumors and
clinically negative axilla, the morbidity from axillary dissection done as a therapeutic or staging modality
can be avoided by careful histological examination of the sentinel lymph nodes identified by various
methods and conducting full axillary dissection only in those with positive sentinel nodes. Sentinel Node
Biopsy (SNB) is performed using 0.3ml sub-dermal injection of patent blue dye or 2% methylene blue 10
minutes prior to the surgical incision and 0.5ml of technetium–labeled sulphur colloid 2 hours prior to
surgery. The technique should be validated in each centre for its sensitivity and specificity before offering
it as a routine. Low axillary sampling, an alternative to SNB can be practiced more widely in developing
countries. If histological evaluation of sentinel lymph nodes or low axillary sampling does not reveal any
metastasis, completion axillary clearance is not warranted. However, if the SNB is positive or the paraffin
sections show metastasis, completion axillary clearances (Level I – III) are generally considered. There is
however recent EORTC-AMAROS RCT showing that in SNB + ve cases, axillary RT achieves axillary
control rates similar to completion axillary clearance but with different morbidity pattern (Donker et al,
Lancet Oncol. 2014).
Breast reconstruction: In centres with such expertise, breast reconstruction should be offered to women
who are likely to have a poor cosmetic outcome after BCT or are undergoing mastectomy and not at
excessive risk of local recurrence or wound complication. Because of the resource constraints and optional
nature of this service, few centres in the country, especially in the busy public hospitals, routinely offer
or perform breast reconstructions for majority of the patients who may benefit from such reconstruction.
Hence good quality breast reconstruction services may be prioritized.
Whole breast reconstruction (WBR) with or without nipple areolar reconstruction should be offered to
motivated young women who have to undergo a mastectomy for a DCIS or early breast cancer (for reasons
such as diffuse micro-calcification or multi-centric disease) or as a prophylactic surgery as in BRCA1
mutation carriers. Reconstruction could be immediate or delayed. WBR can be done with pedicle flap
(Latissimus dorsi flap with implant or expander or a Transverse Rectus Abdominis Myocutaneous flap)
or as a Free flap with microvascular anastomosis (Deep Inferior Epigastric perforator flap; Anterolateral
thigh flap or Superior Gluteal artery perforator flap)
Partial breast reconstruction (PBR): Is indicated after upfront surgery for large tumor with micro-calcification
or after NACT with unfavourable breast to tumor ratio and patient is keen on breast conservation.
Reconstruction can be done using autogenous tissue (fat, muscle, skin and vasculature) from the back
(latissimus dorsi flap), abdomen or thigh as a free or pedicled flap.

7
CHAPTER
HISTOPATHOLOGICAL EVALUATION AND REPORTING
Optimal management of breast cancers hinges upon standardized histopathology evaluation and
reporting30 .
All specimens should be transported to the pathology lab immediately. In case a delay is expected surgeons
should slice specimen’s posterior aspect upwards.
All lumpectomies should be treated as potentially harboring cancer and should be oriented for margin
evaluation. A six surface margin (anterior, posterior, inferior, superior, medial and lateral) is sufficient for
routine evaluation though more extensive sampling may result in greater margin positivity. Close margins
are to be evaluated radially whereas shave margins should be evaluated for further margins.
All specimens should be fixed in 10% neutral buffered formalin with pH7.2 to 7.4. Sections for ER/
PR/Her2neu estimation should be fixed for no less than 6 hours and no more than 72 hours before
processing. ASCO-CAP guidelines suggest recording the time specimen is out of patients body and
time specimen is fixed in formalin for validating specimen fixation. ASCO-CAP guideline state “It is the
responsibility of the surgeon and operating room staff or the radiologist and his/her staff obtaining the
specimen to document the collection time, and it is the responsibility of the pathologist and laboratory
staff to document the fixation start time”.
For lymph nodes, record t h e number, size of largest node and number of grossly metastatic nodes.
One section from grossly metastatic nodes is enough. For lymph nodes>5mm in maximum size slice
at approximately 3mm or less perpendicular to the long axis. Lymph nodes <5mm should ideally be
bisected and blocked; alternatively, lymph nodes <5mm can be blocked in their entirety. Nodes should be
counted even on microscopy to avoid duplication of nodes during submission.
For sentinel node, slice at 2mm interval and submit entirely. If the initial H&E stained section is negative,
four levels are cut. Three of these sections are stained by H&E and one randomly chosen section is
stained with an epithelial IHCstain.
Sections to be taken
Lumpectomy
A: Four sections from tumor all with adjacent normal breast;
B to G: Six surface margins;
H: Remaining Axillary /apical nodes
Mastectomy
Specimens are evaluated similarly but base is the only relevant margin.
Nipple areola and overlying skin should be evaluated whenever included in specimen.

All mammographically detected lesions should be grossed under mammographic guidance. Make sure
to block the entire lesion so as that the size of lesions can be reconstructed microscopically. Also sample
margins of lesions radiologically.
Essentials in a Histopathology report:
•• Tumor size (all 3 dimensions)
•• Tumor type
•• Tumor grade (Modified Richardson Bloom Score)
•• Presence of extensive intraductal carcinoma (EIC)*
•• Lymphovascular emboli
•• Margin status (negative /close /focal positive /gross positive) in wide excision**
•• No.of metastatic nodes and total axillary lymph node dissected
•• Receptor status: ER and PR (by IHC or EIA) and HER2neu by IHC. ER and PR should be scored as
described later.**
•• HER2neu of 2+ on IHC is considered equivocal and this can be resolved by FISH test for gene
amplification, which is considered amplified or positive if score >2.2.
*EIC: DCIS in >25% of any low power field within or outside the tumor. It is a strong predictor of local
recurrence after BCT, especially if margins are positive.
**Gross +ve cut margin: Extensive involvement of a cut margin OR >3 foci of invasive or in-situ carcinoma
in any inked margin. It requires revision excision or mastectomy.
**Focal positive cut margin: 3 or less foci of invasive or in-situ carcinoma in any inked margin. It requires
revision surgery especially if EIC is present
Modified Richardson Bloom grading system (Nottingham’s modification)
Tubule Nuclear grade Mitosis/10hpf*
Score1 >75% Small uniform nuclei, no pleomorphism 0-6
Score2 10-75% Moderate sized nuclei with pleomorphism 7-12
Score3 <10% Marked pleomorphism >12
Final score 3-5=Grade I, Final Score 6-7=Grade II, Final Score 8-9=Grade III
*Could vary with microscope.
•• Grade all carcinomas, including post NACT, special types and core biopsies.
•• ER/PR estimation should be routinely performed. ERPR expression in >1% of cells is reported
as positive for hormone receptors. For ER/PR estimation it is crucial to fix tissues in 10% neutral
buffered formalin and employ pressure cooking methods for antigen retrieval. When reporting on
outside referral material, if fixation procedure is not documented, poor quality of fixation, if evident,
should be commented. Though ASCO-CAP guidelines suggest that such samples should be rejected,
it is not feasible in many Indian practice settings. Including normal breast tissue along with tumor
section helps to asses internal control for hormone receptor and validate a given test result31,32.

•• Her2neu IHC testing should ideally be done by the FDA approved Hercep test OR Ventana Her2neu
assay. However these FDA approved assays are not commonly used in India due to their cost. Hence
before using any non validated antibody in routine practice, the laboratory should validate it either
with FISH or the FDA approved IHC assays. Any Her2neu IHC showing membranous staining
of normal breast epithelium should be reevaluated. Since patients with IHC score 3 may receive
Trastuzumab without FISH confirmation, strict guidelines for interpretation and reporting should be
followed. Only a complete and crisp membrane staining without any cytoplasmic staining in >30%
of cells should be interpreted as score 3 or positive. Score 2 staining results in complete membrane
staining but in <30% of cells and considered equivocal. All other staining is negative (score1/0). For
FISH, count non overlapping cells and select block for invasive tumor. Reject FISH if signals are non-
uniform, background obscures interpretation, autofluorescence33.
•• Ki67 correlates with tumour grade and can provide useful additional prognostic information in low
grade tumours. Validated Ki67/MIB1 testing in node negative, small, low grade tumours can help
decide the need for chemotherapy in such cases.

8
CHAPTER
SYSTEMIC THERAPY
S
ome form of systemic therapy with either hormone therapy, chemotherapy or targeted therapy in
various combination and sequences is offered to almost all breast cancer patients. The choice of
systemic therapy and combination of systemic therapy used in modern practice is based on large
RCTs consisting of several thousand patients and meta-analysis and is outlined here.
Systemic Therapy (Levels of Evidence in Parentheses) in OBC/ LOBC/LABC
Adjuvant following surgery in OBC NACR# for LOBC/LABC##
Node negative Node positive
*Chemotherapy (1) OR ***Chemotherapy (1) ****Chemotherapy ®Surgery (1)

**Only endocrine therapy (1) OR
****Adjuvant endocrine therapy for ER and/or PR + ve after completing chemo (1)
******Adjuvant trastuzumab (if feasible) after anthracycline or concurrently with taxanes in patients
with HER2 positive disease (1)
*Six cycles of an anthracycline regimen (FEC-90-100 or FAC) is a standard regimen in node negative
patients. Taxanes may be added in some high risk patients (high grade, triple negative or HER2 positive).
CMF is an option in some patients with cardiac risk and/or some elderly women34.The benefit of adjuvant
chemotherapy in node negative breast cancer, both in premenopausal and postmenopausal patients has
been established in large EBCTCG meta analyses. A number of risk stratification schemes such as the St
Gallen’s5 and Adjuvant Online! can be used to decide adjuvant chemotherapy. A number of tests using
multigene classifiers such as Recurrence Score and Mamma print are available but are yet to be validated
in prospective randomized studies and are expensive. Therefore their routine use for decision making
is not recommended. Recently IHC4 test (ER, PR, HER2 &Ki-67) has been shown to provide similar
information. However standardization of Ki-67 is a matter of concern for its routine use.
**Patients with small (<2cm), node negative, ER or PR positive, HER2 negative, low grade tumors may
be considered for adjuvant endocrine therapy alone5. Performance of a locally standardized marker of
proliferation such as Ki-67 can further aid in selecting low proliferative tumors in whom chemotherapy
may be avoided.
***Six to eight cycles of a standard anthracycline-taxane regimen (AC/EC-paclitaxel/docetaxel, FEC-
docetaxel, TAC, etc) is standard adjuvant chemotherapy for node positive breast cancer. Consider
weekly or every 2-week scheduling for paclitaxel and every 3 week scheduling for docetaxel.35 Docetaxel

based chemotherapy and dose dense anthracycline/paclitaxel (2 weekly) based chemotherapy should be
supported with prophylactic G-CSF support.
****Anthracycline and taxane regimens are standard NACT regimens in LABC. Surgery can be
sandwiched between pre- and post-operative chemotherapy or in responding tumours, all chemotherapy
can be pre-operative, as per institutional practice.
*****Tamoxifen for five years in pre-menopausal women is standard adjuvant endocrine therapy. Aromatase
inhibitor (AI) containing regimens (Tam-AI switch or 5 years of AI) constitute standard adjuvant endocrine
therapy in post-menopausal patients. The ATLAS trial has now established the role of tamoxifen beyond
5 years and this option should be offered to those with high recurrence risk (Lancet. 2013;381:805–
816). Consider extended adjuvant therapy with letrozole after 5 years of tamoxifen in node positive post-
menopausal women. Tamoxifen for 5 years is an acceptable alternative in post-menopausal women36,37.
******Adjuvant trastuzumab, if feasible, improves outcome in patients with HER2 positive non-metastatic
breast cancer. As most trials have used it for 1year, this duration is considered standard as per current
international guidelines. However, one small trial that used adjuvant trastuzumab for 9 weeks also showed
a trend towards improved outcome. Therefore 9-12 weeks of adjuvant trastuzumab preferably given
with concurrent taxane followed by 4 cycles of anthracycline based regimen can also be considered
an acceptable alternative. Addition of trastuzumab to neoadjuvant chemotherapy should be considered
in view of improved outcome in randomized trials38-40. When not feasible, the use of chemotherapy
(preferably anthracycline based) without traztuzumab is an acceptable alternative in patients with HER2
over-expressing tumors.

9
CHAPTER
RADIOTHERAPY
P
ostoperative RT using Linac or telecobalt to the breast/ chest wall with or without lymphatic areas
is indicated in most cases, except after mastectomy for a DCIS or early node negative cancer.
Several large R C Ts have shown that post mastectomy radiotherapy in women with T3-4, N+
cancers, improve loco-regional control as well as survival41,42 Large randomized trials have also shown
that radiotherapy after conservative surgery is integral in achieving loco-regional control comparable to
mastectomy and with improved body image43,44 . The aim is to use an appropriate technique for safely
giving adequate doses of radiation, equivalent to 50Gy/25#/5weeks, to control subclinical disease in
tissues at risk (chest wall/ breast+/-SCF).
A. Indications for postoperative Radiotherapy
Post Mastectomy RT (PMRT) to chest wall +/- nodal area
•• >3 axillary nodes positive
•• Any number of nodes positive after NACT
•• Clinically or Pathologically T3 or T4 Tumour
•• Positive resection margins
•• Known residual disease in axilla
•• Initial involvement of SCF/IMC
•• For 1-3 nodes +ve, PMRT is being increasingly considered following recent EBCTCG metaanalysis
(McGale et al. Lancet. 2014), which showed improvement in breast cancer specific mortality. With
routine use of more effective chemotherapy, the absolute benefit of PMRT in patients with 1-3 node
+ve but smaller tumours with favourable features is likely to be less and may be individualized based
on age and comorbidity.
After Breast Conservative Surgery: All cases of BCT require postoperative RT. However, RT may be
avoided in selected elderly women with small, node –ve, low grade, ER/PR+ve tumours with low risk of
recurrence as seen in the recent PRIME trial (Kunkler et al Lancet Oncology, 2015)
IMC RT: RT to IMC fell into disuse after its associated excess cardiac mortality became evident. Two
recent RCTs - EORTC (Poortman et al, NEJM 2015) and MA-20 (Whelan et al, NEJM 2015) evaluating
the role of RT to SCF plus IMC in patients with medial or central quadrant tumours or those with axillary
node +ve, showed a modest improvement in DFS but no difference in overall survival. Moreover, the
contribution of IMC RT in the very modest benefit with SCF plus IMC RT is likely to be even smaller.
In addition there are technical challenges in planning and delivering cardiac safe IMC RT. Hence most
centres around the world continue to offer IMC RT only for cases with radiological or pathological
evidence of IMC node involvement.

Axilla: It is a common practice in many Indian centres to treat axilla for all node +ve cases, possibly due
to sub-optimal axillary surgery or histopathological evaluation in practice settings. As post-op axillary
RT can increase arm & shoulder morbidity, it is advocated for residual axillary disease or node +ve after
inadequate axillary surgery and revision surgery is not being considered for various reasons. Recently the
EORTC-AMAROS trial (Donker et al, Lancet Oncol. 2014) shows that in T1-2 clinically node negative
with sentinel node biopsy +ve, axillary RT results in excellent disease control comparable to completion
axillary dissection but with different morbidity pattern.
B. Treatment Area and Technique for Radiotherapy
1. Chest wall: Bitangential portals, isocentric or with breast cone. Bolus if skin was involved or at high
risk of recurrence. For left sided tumours, minimize cardiac dose with appropriate beam angulation and
cardiac shielding if required.
2. Whole Breast: Bitangential portals; Isocentric, with appropriate wedges. 3DCRT or IMRT if large
breasts to reduce acute/late toxicity in areas of dose inhomogeneity. LINAC preferable but Telecobalt can
be used if Interfiled separation is <18cm & breast is not large. Avoid cardiac dose with beam placement
or cardiac shielding.
3. SCF (in axillary N+ cases or initial SCF involvement): Direct anterior portals, avoiding overlap with
tangents to prevent matchline fibrosis and rare occurrence of brachial plexopathy.
4. Axilla: When indicated, axilla can be irradiated with an anterior extended SCF field with posterior
axillary boost.
5. IMC (in known IMC involvement): CT planned partially wide tangents or mixed electron/photon ports
on LINAC.
6. Tumor Bed boost (In all cases of BCT except for DCIS and in postmenopausal women with small
tumors with favorable histology and-ve margins): Enface electrons, 3D CRT or in selected cases, HDR
brachytherapy in expert centres.
C. Radiotherapy dose and fractionation
50Gy in 25 daily fractions over 5 weeks or its equivalent hypofractionated regime of 40Gy/15 fractions
over 3 weeks or 42.5Gy/16# over 3 weeks45,46. Hypofractionated regimen is equivalent to the conventional
regimen in terms of disease control and survival. These hypofractionated regimens results in significantly
lower incidence of acute and late breast toxicity and without excess cardiac morbidity at 15 year. The 3
week hypofractionated regime has become the standard of care in the UK, Canada and many large volume
Indian centres for BCT and post mastectomy RT. For hypofractionated regimes, appropriate planning
should be done to minimize dose inhomogeneity and cardiac dose. Tumor Bed Boost after whole breast
RT for BCT is given with appropriate energy electrons or 3DCRT photons to a dose of 10–16Gy with
2-2.5 Gy per fraction. For HDR boost a twice daily regimen of 4.5 - 5 Gy x 2 or 3.4Gy x 3 fractions.
D. Accelerated partial breast radiation (APBI)
This short and convenient course of RT has been tested in several large RCTs which are yet to report
long-term results. Hence it should be considered an investigational approach. Currently, centres with
experience are offering APBI to carefully select postmenopausal women with node negative, small tumors
with clear margins and no adverse pathological features47. A recent European RCT compared multicatheter
interstitial APBI with whole breast RT + boost in 1184 women >40 years of age with up to 3 cm tumour,
pNo or pNmi. It shows equivalent disease control and survival at a median follow up of 6.6 years (Strnad
et al, Lancet, 2015) and this was evident in all age groups above 40 years and in all tumor types.
E. Palliative Radiotherapy is described in the chapter of metastatic disease.

10
CHAPTER
FOLLOW UP
Patients and their families should be counseled on the need for regular follow up in order to
1. Timely detection and salvage of loco-regional recurrences
2. Timely detection and treatment of contralateral breast caner
3. Detect and treat metastatic disease when symptomatic and prevent its complications.
4. Monitor and manage any late sequelae of treatment including those of treatment induced
menopause.
5. Address any quality of life and survivorship issues arising in subsequent years.
At follow up visits take detailed history, especially of any metastatic symptoms or physical or psycho-
social sequelae of treatment or menopausal symptoms. Clinical examination is complemented with
mammogram (bilateral if BCT has been done) every 12 – 24 months. Randomized trials48,49 have shown
that regular follow up laboratory or radiological investigations does not improve survival or quality of life
hence they are not recommended.
The follow-up frequency suggested in the first 5 years is every 6 months or earlier if any symptoms.
Subsequent visits could be annual up to10 years and then 2 yearly.
Patients with significant family history of cancer or known BRCA mutation should be kept on lifelong 6
monthly or annual follow up as they have a much higher risk of contralateral breast cancer and ovarian
cancer. Cancer screening and prevention strategies for these women is described later.

11
CHAPTER
METASTATIC BREAST CANCER
T
he metastatic disease may be symptomatic or asymptomatic and detected at initial presentation
or during follow up. The overarching goal of managing metastatic breast cancer is to allow the
patient to regain and maintain the best possible quality of life and to prolong her life to the extent
possible. This requires careful assessment and documentation of cancer associated symptoms, previous
treatment history along with the nature, extent and tempo of loco-regional and metastatic disease. In
addition to assessing prognostic and predictive factors like ER/PR and HER2neu, patient’s physiological,
psychological and financial reserve and support system should also be assessed. This helps in providing
individualized holistic care which could range from intensive chemotherapy to only best supportive care,
in consultation with the patient and the family. As most Indian centres do not have a specialized palliative
care unit, the treating oncologist will be required to provide symptom control including pain control using
pharmacological and non-pharmacological approaches.
11.1 Management algorithm (Levels of Evidence in Parentheses)
Detailed History and physical examination including Performance Status (PS) and co-morbidities along
with routine blood tests and imaging (plain radiographs, ultrasound, CT scan, bone scan, PET-CT scan)
is done as appropriate
Poor PS/significant co-morbidities Poor PS/Minimal or no comorbidities
Endocrine therapy if HR (hormone receptor) positive*

Best supportive care HR + HR -
Bone &/or soft tissue mets Visceral mets Short DFS
Oligo-visceral metastasis High burden
**Chemotherapy (1)
*Hormonal Therapy (1) **Chemotherapy (1)

****± Bisphosphonates (1) ***± HER2-targeted therapy if HER2 positive (1)
± RT to symptomatic / weight bearing sites ± Bisphosphonates ± RT if symptomatic bone mets
Hormone Refractory
Document the site and extent of metastatic disease and loco-regional disease if any. Measurable lesions
should be specifically documented for response assessment.

Initiate counseling, pain control, medication and symptom control measures as required. Early referral to
palliative care unit is desirable.
NOTES
*Hormonal Therapy50,51,58
•• Premenopausal–Tamoxifen. On progression consider ovarian suppression followed by aromatase
inhibitors (AI).
•• Postmenopausal - Aromatase inhibitor or Tamoxifen. On progression, tamoxifen, fulvestrant or other
AI.
**Chemotherapy52-55,58
•• Combination chemotherapy is preferred in patients with high visceral burden and in other cases
single agents can be used.
•• Longer duration of chemotherapy for metastatic breast cancer is associated with modest improvement
in overall and progression free survival. Chemotherapy duration should be individualized.
•• Anthracyclines or taxanes are the preferred first line agents if they have not been used earlier.
In anthracycline and taxane pretreated patients consider capecitabine, platinum, rechallenge with
taxanes including nano paclitaxel versions, vinorelbine, gemcitabine and ixabepilone.
***HER2 Targeted therapy56,58
•• In HER2 positive patients consider trastuzumab, lapatinib or their combination in addition to
chemotherapy if it is feasible.
****Bisphosphonates57,58
•• Patients with bone metastases should be considered for regular intravenous bisphosphonates like
zoledronic acid 4mg every 4 weeks with RFT monitoring.
Mastectomy
In patients with metastatic disease, mastectomy is considered for palliation of symptoms such as fungation
or bleeding, especially when locoregional disease is progressing on systemic therapy and is still resectable
with primary skin closure. For patients with isolated or few metastasis (oligo-metastasis), role of definitive
loco-regional treatment is uncertain. A recent Indian RCT has shown that locoregional treatment in such
patients does not improve survival (Badwe et al. Lancet Oncology, 2015).
Palliative Care
In patients with metastatic disease, the patient should be referred to the palliative care unit or pain clinic
at the earliest. Not only this helps to achieve prompt symptom control but the quality of life is better
maintained with holistic care. If a specialized palliative care unit is not accessible, the treating oncologist
should provide comprehensive care and symptom control including pain control. Availability of morphine
is still an issue in some parts of the country.

Palliative Radiotherapy
Bone metastasis
Radiotherapy along with Bisphosponates is the main stay of treatment for symptomatic bone
metastasis.
For isolated or few bone metastases, the affected bones with some margins is irradiated with 8Gy single
fraction at the earliest possible opportunity59.
Fractionated radiotherapy of 20Gy/5# or 30Gy/10# should be considered in patients with impending
fracture or cord compression60 Established fractures in patients with at least few months of life expectancy
should be fixed surgically and then given postoperative RT. For patients with widely disseminated and
symptomatic bone metastasis in whom chemotherapy is not indicated immediately, Hemi Body Irradiation
(HBI) as single dose of 6Gy Upper HBI or 8Gy Lower HBI, produces excellent symptom relief 61. If both
Upper and Lower HBI are required, the more symptomatic half should be treated first and a gap of 4-6
weeks should be maintained to allow the marrow to recover. After HBI, chemotherapy should be deferred
for 4-6 weeks or longer to prevent severe myelosuppression. Upper HBI should be avoided in patients
with compromised lung function.
Brain metastasis
Most symptomatic patients would benefit from steroids and fractionated Whole brain RT (WBRT)62.
Recommended dose is 20Gy/5#/1week or 30Gy/10#/2weeks. The MRC trial had shown that in
patients with poor GC and widely disseminated disease, 12Gy in 2 fractions on consecutive days (or 1
week apart) is comparable to 30Gy/10#/2 weeks (Priestman et al, Clin. Oncology, 1996).
For single brain metastasis in patients with controlled primary and no other site of systemic disease,
consider surgery or radiosurgery of the brain lesion followed by whole brain radiotherapy. Recent NCCTG
trial (ASCO 2015) shows that in patients with 1-3 brain metastases, addition of WBRT to SRS improved
intracranial control without improving survival and with adverse impact on cognitive function. SRS alone
should be judiciously used in highly select patients.
Spinal cord compression
Palliative Radiotherapy (20Gy/5# or 30Gy/10#) with steroids is the mainstay of treatment. Select cases
with life expectancy of more than 6 months presenting with recent onset paraparesis or paraplegia
and limited vertebral involvement should be considered for surgical decompression prior to palliative
radiotherapy.

12
CHAPTER
HEREDITARY BREAST CANCER
H
ereditary cancer accounts for 5% of all breast cancers and a greater proportion of ovarian
cancers. Germline mutations in two breast cancer susceptibility genes BRCA1 and BRCA2
account for over 50% of the Hereditary Breast Ovarian Cancer (HBOC) families. Mutation in
TP53 gene accounts for a small fraction of families, as part of Li-Fraumeni syndrome.
Clinico-pathological features of hereditary breast cancer
•• Younger age at diagnosis (1-2 decade earlier)
•• Greater propensity for multi-focal involvement
•• High probability (50%) for synchronous or metachronous bilateral breast cancer
•• BRCA1 associated breast cancers have a distinct genetic signature of Basal Type with preponderance
of poorly differentiated ER, PR and HER2-ve (Triple negative) tumours.
A genetic risk assessment and referral for genetics evaluation should be considered in:
•• Early onset breast or ovarian cancer, especially if it is triple negative breast cancer
•• Personal history of bilateral breast, or bilateral ovarian cancers.
•• Personal history of primary breast and ovarian cancer in the same individual.
•• Personal history of breast or ovarian cancer, along with family history of one or more family members
with breast, ovarian or some other cancer.
•• A known BRCA1 or BRCA2 mutation in a blood relative.
•• Member of an ethnic community with known founder BRCA1/2 mutation.
•• Any women concerned about her hereditary cancer risk
Genetic Testing using BRCA1/2 gene sequencing recommended for women with strong family history of
early onset breast and or ovarian cancer or when the calculated probability of finding a BRCA mutation
is >10%8.
There are very limited centres for comprehensive genetic counseling, genetic testing and medical
management of carriers in India. One such centre is the ICMR Centre for Advanced Research i n C a n c e r
G e n e t i c s at ACTREC, Tata Memorial Centre in Mumbai ([email protected]).
Screening for women from HBOC families or known BRCA mutation carriers should start at the age of
25 years or 5 years before the youngest affected member in that family, whichever is earlier.
•• Monthly breast self examination
•• Six monthly clinical breast examination

•• Annual breast imaging. Due to dense breasts in these young women, clinical examination,
mammography and ultrasound all have poor sensitivity. In experienced centres, MRI has much higher
sensitivity for detecting breast cancer in such women2.
•• With no clear benefit of ovarian cancer screening with Transvaginal USG and CA-125, it is not
routinely recommended.
Cancer Prevention: The options for cancer prevention in these high-risk women include chemoprevention
using tomoxifen; Risk Reducing Salpingo-Oopherectomy (RRSO) and Bilateral Prophylactic Mastectomy
(BPM) with reconstruction. The final decision regarding the procedure undertaken is made jointly after
taking into consideration the patient’s wishes after providing full information regarding the pros and cons
of the procedure. The most useful prophylactic procedure is RRSO, at the age of 35-40 years and after
completion of child bearing63. This reduces the risk of ovarian cancer by 99% and of breast cancer by
50%.
Clinical trials of Platinum agents and PARP inhibitors are underway for women with BRCA1/2 associated
hereditary breast or ovarian cancer.

13
CHAPTER
RESEARCH ISSUES
1. Risk factors for breast cancer in Indian women in the context of changing life styles
2. Behaviour of breast cancer in young women as relevant to Indian demography
3. Pragmatic and effective population based screening programmes
4. Opportunistic or targeted screening for high risk or concerned women
5. Standardization and improving quality of radiological, cytological and histopathological diagnosis
and staging of breast cancer.
6. Safety and efficacy of breast conserving surgery in LABC
7. Sentinel node biopsy and axillary sampling
8. Novel techniques and fractionation of radiotherapy to improve cost effectiveness and throughput
9. Role of PET-CT in staging and response assessment
10. Pragmatic and cost effective approaches like primary progesterone
11. Developing strategies for genetic testing, counselling and risk management for hereditary breast
cancer
12. Role of targeted therapies
13. Genomic characterization of breast cancer in Indian women

14
CHAPTER
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CONSENSUS DOCUMENT

Prepared as an outcome of ICMR Subcommittee on

Indian Council of Medical Research,

Dr. Soumya Swaminathan

Dr. V. K. Srivastava : Head (Publication & Information)

Production Controller : JN Mathur

(Dr. G.K. Rath)

(Dr. R.S. Dhaliwal)

Message from Chairperson ii

Preface (Chairperson of Subcommittee) iii

1. Breast Cancer in India and need for Management Guidelines 11

2. Breast Cancer Epidemiology and Screening 13

3. Breast Cancer Staging & Prognostic criteria 14

4. Diagnostic Evaluation and Staging Work up 16

5. Management of Breast Cancer 19

6. Surgery for Breast Cancer 23

7. Histopathological Evaluation and Reporting 24

11. Metastatic breast cancer 32

12. Hereditary Breast Cancer 35

13. Research Issues 37

BREAST CANCER IN INDIA AND NEED FOR MANAGEMENT

11 Consensus Document for Management of Breast Cancer

12 Consensus Document for Management of Breast Cancer

BREAST CANCER EPIDEMIOLOGY AND SCREENING

13 Consensus Document for Management of Breast Cancer

STAGING AND PROGNOSTIC CRITERIA

TNM STAGING SYSTEM (Clinical)

14 Consensus Document for Management of Breast Cancer

TNM STAGING SYSTEM (Pathological)

15 Consensus Document for Management of Breast Cancer

DIAGNOSTIC EVALUATION AND STAGING WORK UP

16 Consensus Document for Management of Breast Cancer

Partly adapted from NCCN/ ESMO/ NICE practice guidelines)4-9

17 Consensus Document for Management of Breast Cancer

18 Consensus Document for Management of Breast Cancer

MANAGEMENT OF BREAST CANCER

19 Consensus Document for Management of Breast Cancer

Histopathological confirmation and Breast Imaging as describe earlier

BCT followed by MRM Followed by

20 Consensus Document for Management of Breast Cancer

Hispathological confirmation and Breast Imaging as described earlier

Metastatic-work-up as described earlier

No metastatic disease Metastatic Disease

Mastectomy with Primary skin closure Follow relevant algorithm

MRM Patient keen Neo-Adjuvant

In responding patients, Complete all No Response

MRM (standard)/BCT (optional)1,2 Mastectomy OR

Completion of Chemotherapy and Adjuvant

21 Consensus Document for Management of Breast Cancer

Wide excision Inadequate MRM

Only If feasible, Revision excision with

22 Consensus Document for Management of Breast Cancer

SURGERY FOR BREAST CANCER

23 Consensus Document for Management of Breast Cancer

HISTOPATHOLOGICAL EVALUATION AND REPORTING

24 Consensus Document for Management of Breast Cancer

25 Consensus Document for Management of Breast Cancer

26 Consensus Document for Management of Breast Cancer

Adjuvant following surgery in OBC NACR# for LOBC/LABC##

Node negative Node positive

11 Consensus Document for Management of Breast Cancer

12 Consensus Document for Management of Breast Cancer

13 Consensus Document for Management of Breast Cancer

14 Consensus Document for Management of Breast Cancer

15 Consensus Document for Management of Breast Cancer

16 Consensus Document for Management of Breast Cancer

17 Consensus Document for Management of Breast Cancer

18 Consensus Document for Management of Breast Cancer

19 Consensus Document for Management of Breast Cancer

20 Consensus Document for Management of Breast Cancer

21 Consensus Document for Management of Breast Cancer

22 Consensus Document for Management of Breast Cancer

23 Consensus Document for Management of Breast Cancer

24 Consensus Document for Management of Breast Cancer

25 Consensus Document for Management of Breast Cancer

26 Consensus Document for Management of Breast Cancer

Chemotherapy (1) OR Chemotherapy (1) **Chemotherapy ®Surgery (1)

27 Consensus Document for Management of Breast Cancer

28 Consensus Document for Management of Breast Cancer

29 Consensus Document for Management of Breast Cancer

30 Consensus Document for Management of Breast Cancer

31 Consensus Document for Management of Breast Cancer

32 Consensus Document for Management of Breast Cancer

33 Consensus Document for Management of Breast Cancer

34 Consensus Document for Management of Breast Cancer

35 Consensus Document for Management of Breast Cancer

36 Consensus Document for Management of Breast Cancer

37 Consensus Document for Management of Breast Cancer

38 Consensus Document for Management of Breast Cancer

39 Consensus Document for Management of Breast Cancer

40 Consensus Document for Management of Breast Cancer