From,
Dr. Ashok Hegde
Professor & HOD Department of General Surgery,
A.J. Institute of Medical Sciences,
Mangalore- 575004
To,
The Member Secretary,
Ethical committee A.J.I.M.S,
A.J. Institute of Medical Sciences,
Mangalore- 575004
Respected sir,
Subject: Submission of Synopsis of Dissertation for Ethical Committee Clearance.
Herewith, I am forwarding the synopsis of the dissertation work of Dr.Nandini.V, Postgraduate Resident in the department of General Surgery , titled :
“A CLINICOPATHOLOGICAL STUDY OF INFILTRATING CARCINOMA OF THE BREAST AND CORRELATION WITH ESTROGEN RECEPTOR[ER] , PROGESTRON RECEPTOR [PR] AND HER2nue STATUS ” for ethical committee clearance of
A.J. Institute of Medical Sciences.
Kindly accept the same and oblige.
Thanking You,
Signature of the head of the department & Guide
(Dr .Ashok Hegde)
Signature of the Postgraduate
(Dr. Nandini.V)
Place: Mangalore
Date: 15/9/13
From,
Dr. Nandini.V
Post Graduate in Department of General Surgery,
A.J. Institute of Medical Sciences,
Mangalore- 575004
To,
The Registrar,
Rajiv Gandhi University of Health Sciences,
Bangalore
(Through proper channel)
Sub: Submission of Synopsis of Dissertation
Respected Sir,
Herewith, I am submitting synopsis of my dissertation work:
“CLINICOPATHOLOGICAL STUDY OF INFILTRATING CARCINOMA OF THE BREAST AND CORRELATION WITH ESTROGEN RECEPTOR[ER] , PROGESTRON RECEPTOR [PR] AND HER2nue STATUS” for the registration in
Rajiv Gandhi University of Health Sciences, Bangalore.
Kindly accept the same and oblige.
Thanking you,
Yours faithfully,
(Dr. Nandini.V)
Place: Mangalore
Date:15/9/13
CURRICULUM VITAE
Name: Dr.Ashok Hegde
Date Of Birth & Age :Jan 24,1963 – 50yrs
Present Designation :Professor & HOD
Department:General Surgery
College:A.J. Institute Of Medical Sciences
City :Mangalore
Residential Address :5th cross, kodialguttu road east
Manglore-575003
Phone & Fax Number With Code :Office :0824-2225533
Residence : 0824-2493951
Mobile :9845132949
PAN Number : AAPPH6495R
Date Of Joining Present Institution: on Oct 16th, 2003 as Professor & HOD
Qualifications:
Qualification / College / University / Year / Registration No. Of UG & PG With Date / Name Of The State Medical CouncilM.B.BS / Kasturba Medical College, Manglore / Mangalore university / June
1985 / 25702
Dt. Jan 12,1987 / Karnataka Medical Council
MS(general surgery) / Kasturba Medical College, Manglore / Mangalore university / Dec
1989 / 25702
Dt. Feb 02 ,2005 / Karnataka Medical Council
3. Details Of The Previous Appointments/ Teaching Experience
Designation / Department / Name of Institution / From DD/MM/YY / To DD/MM/YY / Total Experience In Years & MonthsJr. Resident / General Surgery / Kasturba Medical College, Manglore / Sep 01,1986 / Dec 1989 / 3 Years.
Lecturer / General surgery / Kasturba Medical College, Manglore / Jan 24,1992 / Jan 23,1994 / 2 Years
Assistant Professor / General Surgery / Kasturba Medical College, Manglore / Jan 24,1994 / Jan 23,1997 / 3Years
Associate Professor / General Surgery / Kasturba Medical College, Manglore / Jan 24,1997 / Oct 15,2003 / 6 Years
9 Months
Professor
& HOD / General Surgery / A.J. Institute of Medical Sciences, Mangalore / Oct 16,2003 / Till Date
CURRICULUM VITAE
Name: Dr . Nandini.V
Date of birth: June.17.1989 ; 24yrs
Present designation : PG /Junior Resident
Department: General Surgery
College: A.J Institute of Medical Sciences
City:Mangalore
Nature of appointment:Full Time
Whether belongs to : Others
Present Address of employee : Resident Quarters,
No. 304,
AJIMS Campus
Date Of Joining Present Institution :July, 5, 2013 as PG
Academic qualifications:
Qualification / College / University / Year / Registration No. Of UG & PG With Date / Name Of The State Medical CouncilMBBS / PSG Institute Of Medical Sciences & Research
Coimbatore,
Tamilnadu / The Tamilnadu Dr.MGR
Medical University,
Chennai / Jan
2013 / 101862 / Tamilnadu Medical Council,
Chennai
DM/M. Ch / NA / NA / NA / NA / NA
3. Details Of The Previous Appointments/ Teaching Experience
Designation / Department / Name of Institution / From DD/MM/YY / To DD/MM/YY / Total Experience In Years & MonthsPG/Junior Resident / General surgery / A.J Institute of medical
Science, Mangalore / July 5, 2013 / Till date / 2 Months
SYNOPSIS
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore
“A CLINICOPATHOLOGICAL STUDY OF INFILTRATING CARCINOMA OF THE BREAST AND CORRELATION WITH ESTROGEN RECEPTOR[ER] , PROGESTRON RECEPTOR [PR] AND HER2nue STATUS”
Name of the candidate :Dr. NANDINI.V
Guide :Dr. ASHOK HEGDE
Course and Subject :M.S. (Gen.Surgery)
Department of Gen.Surgery
A J Institute of Medical Sciences,
Kuntikana, Mangalore.
2013
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of the candidate and address (in block letters) / DR.NANDINI.VPOST GRADUATE RESIDENT,(MS)
DEPARTMENT OF GENERAL SURGERY,
A.J. INSTITUE OF MEDICAL SCIENCES,
MANGALORE.
2 / Name of the Institution / A. J. INSTITUTE OF MEDICAL SCIENCES MANGALORE.
3 / Course of study and Subject / M.S GENERAL SURGERY
4 / Date of admission to course / JULY 5, 2013.
5 / Title of the Topic
““A CLINICOPATHOLOGICAL STUDY OF INFILTRATING CARCINOMA OF THE BREAST AND CORRELATION WITH ESTROGEN RECEPTOR[ER] , PROGESTRON RECEPTOR [PR] AND HER2nue STATUS”
- BRIEF RESUME OF INTENDED WORK
Globally breast carcinoma is the leading cause of cancer related death in women worldwide. Despite the high incidence rates, in Western countries, 89% of women diagnosed with breast cancer are still alive 5 years after their diagnosis, which is due to early detection and treatment . The UK and USA have one of the highest incidence rates worldwide (together with the rest of North America and Australia/NewZealand), making these countries a priority for breast cancer awareness. In urban India breast cancer accounts for about 25% to 33% of all cancers in women.Gender is by far the greatest risk factor. Breast cancer occurs 100 times more frequently in women than men. In women, incidence rates of breast cancer rise sharply with age until ages 45 to 50, when the rise becomes less steep. This change in slope probably reflects the impact of hormonal change (menopause) that occurs about this time. Over 50% breast cancer patients in India present in stages 3 and 4, which will definitely impact their survival and the overall 5 year survival for breast cancer patients in India doesn't appear to be even 60% presently.
Over the last few decades there have been outstanding advances in breast cancer management leading to earlier detection of disease and the development of more effective treatments resulting in significant declines in breast cancer deaths and improved outcomes for women living with the disease. Breast cancer is no longer seen as a single disease but rather a multifaceted disease comprised of distinct biological subtypes with diverse natural history, presenting a varied spectrum of clinical, pathologic and molecular features with different prognostic and therapeutic implications. Consensus regarding the definitive prognostic/predictive analysis has yet to be reached, but significant progress continues to be made in the ongoing search for a specific, rigorous and reproducible method of identifying successful treatment algorithms utilizing biological markers.
A number of molecular markers have been identified in invasive breast cancers that have predictive as well as prognostic value. Well known markers include the estrogen receptor α (ER) and progesterone receptor (PR) which are associated with improved outcomes and respond to hormone therapy. HER-2/neu is a tyrosine kinase receptor related to the epidermal growth factor receptor family. Over expression of HER-2/neu in invasive carcinoma is correlated with decreased relapse-free and overall survival, and resistance to hormonal and cytotoxic therapy. Estrogen and progesterone and HER-2 protein play a central role in regulating growth kinetics of breast tissue and are powerful predictive markers. About 75% of all breast cancers are “ER positive”, They grow in response to the hormone estrogen. About 65% of these are also “PR positive”; They grow in response to another hormone, progesterone. About 20% to 25% of breast cancers, the cancer cells make too much of a protein known as HER2/neu. These breast cancers tend to be much more aggressive and fast-growing.
6.2 REVIEW OF LITERATURE
1) A nationwide, population-based, case-case design of 2,640 Swedish women who were 50 to 74 years old and had postmenopausal breast cancer during 1993 to 1995. Follow-up was conducted until 31 December 2000. Using a polytomous multiple logistic regression to investigate the relationships between menstrual factors (age at menarche, cycle length, irregular menstruation, lifetime number of menstrual cycles, and age at menopause), tumor characteristics (size, grade, estrogen receptor and progesterone receptor [PR] status, lymph node involvement, and histology), and Cox proportional hazards modeling for 5-year survival.
2) Li et al reported that women using unopposed estrogen replacement therapy (ERT) had no appreciable increase in the risk of breast cancer. However, use of combined estrogen and progestin hormone replacement
therapy had an overall 1.7-fold (95% CI 1.3–2.2) increased risk of breast cancer, including a 2.7-fold
(95% CI 1.7–4.3) increased risk of invasive lobular carcinoma, a 1.5-fold (95% CI, 1.1–2.0) increased risk of invasive ductal carcinoma, and a 2-fold (95% CI 1.5–2.7) increased risk of ER1/PR1 breast cancers
3)In 1982 A group of 122 consecutively treated pathologic Stage 1 (TINOMO) patients with cancer of the breast were studied to define histopathologic predictors of recurrence. Lymphatic invasion was the most significant predictor of recurrence; recurrence was present in 32% (8/25) of patients who had lymphatic invasion and in 10.3% (10/97) of patients who did not (P = 0.006). Histological type was also predictive of recurrent disease. Eighteen per cent (18/101) of patients with invasive ductal or lobular carcinoma developed recurrent disease, while none of the group of 21 patients with medullary carcinoma, tubular carcinoma, colloid carcinoma, Paget's disease, and intraductal carcinoma with minimal invasion suffered a recurrence.
4) In 1984 Oestrogen receptors were measured in the primary breast tumors of 508 patients and progesterone receptors in those of 486 patients. Survival from mastectomy was significantly longer in patients with receptor-positive tumours. There was no significant difference between patients with receptor-positive and receptor-negative tumours in the relapse-free interval, but survival from first relapse was longer in patients with receptor-positive tumours. Axillary node status and tumour size indicated the probability of relapse but did not influence the length of survival after relapse. Patients who did not respond to hormone therapy and had receptor-positive tumours had the same survival characteristics as those with receptor-negative tumours who did not respond.
5) A 7-year retrospective study of 1134 invasive breast cancer subjects. Clinical and pathologic features and survival of the four subtypes were compared. Using ER/PR+ and Her2− as a reference, ER/PR−, Her2− had the worst overall survival (hazard ratio, 1.8; 95% confidence interval and the worst disease-free survival . In ER/PR+, Her2−, chemotherapy conferred significant overall and disease-free survival advantages. Subtype comparison revealed statistically significant differences in outcomes.
6.3 OBJECTIVES
1) To study the occurrence of ER ,PR & HER2/nue receptors in a core needle biopsy or post surgical histopathology specimen.
2) Correlation of the above findings with other clinical features like – age ,parity, age of menopause, examination findings.
7. MATERIALS AND METHODS
History
A detailed history of every patient is taken including the age, age of menarche, parity, age of menopause, onset and symptoms of the breast lump, significant family history, history of contraceptive use, etc.
Examination
The patient is examined in detail including bilateral breasts, the tumor and lymph nodes are noted.
Histopathology
The surgical or biopsy specimen is sent for grading according to modified Scarf-Bloom-Richardson grading and Immunohistochemistry for estrogen receptor, progesterone receptor & HER2/nue status.
7.1 SOURCE OF DATA
A study to be carried out in female patients coming to the general surgery department of AJ Hospital, Mangalore between August 2013 to January 2015. Considering around 50 women with suspected breast carcinoma not treated with hormone therapy, chemotherapy or radiotherapy.
7.2 METHODOLOGY OF STUDY
- Definition of study subject:
- Inclusion criteria:
- Exclusion criteria:
2) Those who have undergone chemotherapy and/or Radiotherapy.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY
- ROUTINE INVESTIGATIONS REQUIRED:
- SPECIAL INVESTIGATIONS REQUIRED:
- Core needle biopsy, immunohistochemistry.
Clearance obtained
7.5 LIST OF REFERENCES
1) Orgéas CC, Hall P, Rosenberg LU, Czene K.Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Stockholm, SE-17177, Sweden.
2)Li C, Malone K, Porter P, et al. Relationship between long durations and different regimens of hormone therapy and risk of breast cancer. JAMA.2003;289:3254–3263.
3) Am J Clin Pathol. 1982 Dec;78(6):817-20.Roses DF, Bell DA, Flotte TJ, Taylor R, Ratech H, Dubin N.
4) A. Howella, b, R.N.L. Harlanda, b, V.H.C. Bramwella, b, R. Swindella, b, D.M. Barnesa, b, J. Redforda, b, M.J.S. Wilkinsona, , D. Crowthera, b, R.A. Sellwood Departments of Medical Oncology and Clinical Research, Christie Hospital, Manchester, United Kingdom,and Department of Surgery, University Hospital of South Manchester, United Kingdom
5) Adedayo A. Onitilo, MD, MSCR, FACP, Jessica M. Engel, MSN, FNP-BC, Robert T. Greenlee, PhD, and Bickol N. Mukesh, PhD
6) Glass AG, Lacey JV Jr, Carreon JD, Hoover RN. Breast cancer incidence, 1980–2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst 2007;99:1152–1161.
7) Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, Edwards BK, Berry DA. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 2007;356:1670–1674.
8) Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006;295:2492–2502.
9) Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sørlie T, Dai H, He YD, van’t Veer LJ, Bartelink H, van de Rijn M, Brown PO, van de Vijver MJ. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A 2005;102:3738–3743.
10) Dolled-Filhart M, Rydén L, Cregger M, Jirström K, Harigopal M, Camp RL, Rimm DL. Classification of breast cancer using genetic algorithms and tissue microarrays. Clin Cancer Res 2006;12:6459–6468.
11) Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 2007;356:217–226.
8.PROFORMA:
Name of the patient: Age: Sex:
IP NO: Date of Admission:
Chief complaints:
History of presenting illness:
Past history:
Menstrual & Obstetric history:
History of contraceptive usage: yes/no
History of smoking/alcohol intake:
General physical examination:
Pallor/icterus/cyanosis/clubbing/edema
Lymphadenoplthy: Number: Site:
Size: consistency:
Vitals:
BP: PULSE: RR: TEMP:
LOCAL EXAMINATION: BREAST
RT LT
Position
Size and shape
SKIN Colour
Texture
Engorged veins
Ulcer
Nodule
NIPPLE:
AREOLA:
ARM/ AXILLA/THORAX:
Systemic examination:
9. Signature of the candidate
10. Remarks of the guide
11.Name and designation of
11.1 Guide / Dr. ASHOK HEGDE, M.B.B.S, M.S
PROFESSOR & HOD,
DEPARTMENT OF GENERAL SURGERY,
A.J. INSTITUTE OF MEDICAL SCIENCES
MANGALORE
11.2 Signature
11.3 Head of the department / DR ASHOK HEGDE M.B.B.S, M.S
PROF. & HEAD,
DEPARTMENT OF GENERAL SURGERY,
A.J. INSTITUTE OF MEDICAL SCIENCES
MANGALORE
11.4 Signature
12.1 Remarks of the Chairman and Principal
12.2 Signature
INFORMED CONSENT
A J INSTITUTE OF MEDICAL SCIENCES,
KUNTIKANA, MANGALORE
Informed consent form for the patients of “A.J Institute of Medical Sciences Kuntikana, Mangalore”, who will be participating in the research project (MS dissertation) titled “A CLINICOPATHOLOGICAL STUDY OF INFILTRATING CARCINOMA OF THE BREAST AND CORRELATION WITH ESTROGEN RECEPTORL[ER] , PROGESTRON RECEPTOR [PR] AND HER2nue STATUS”
Name of Principal Investigator / Dr. Nandini.V
Junior Resident.
Name of Organization / Department of General Surgery,
A.J Medical Sciences, Kuntikana, Mangalore
This Informed Consent Form has two parts:
- Information Sheet (to share information about the research with you)
- Certificate of Consent (for signatures if you agree to take part)
PART I: Information Sheet
Introduction
I, Dr.Nandini.V, Junior Resident in the department of General Surgery, A.J Institute of Medical Sciences, Kuntikana, Mangalore, is working on my MS dissertation titled “A CLINICOPATHOLOGICAL STUDY OF INFILTRATING CARCINOMA OF THE BREAST AND CORRELATION WITH ESTROGEN RECEPTORL[ER] , PROGESTRON RECEPTOR [PR] AND HER2nue STATUS” My study subjects will be female patients with suspected breast carcinoma admitted in the Surgery department of AJIMS.
I am going to give you information and invite you to be part of this research. You do not have to decide today whether or not you will participate in the research. Before you decide, you can talk to anyone you feel comfortable with about the research. Your decision to participate or not to participate will not have any effect on your treatment in our hospital. There may be some words that you do not understand. Please ask me to stop as we go through the information and I will take time to explain. If you have questions later, you can ask them and get yourself clarified.
Purpose of the research
To assess and determine the role of estrogen receptor[ER], progesterone receptor [PR] & HER2/nue receptor status in deciding the choice of further management of patients with breast carcinoma.
Type of Research Intervention
It is a hospital based prospective study. All the patients admitted for suspected breast carcinoma in the Surgery department of AJIMS in a time period of two years will be enrolled in this study after providing informed consent to participation.
Participant selection
All the patients admitted for suspected breast carcinoma in Surgery department of AJIMS.
Voluntary Participation
Your participation in this research is entirely voluntary. It is your choice whether to participate or not. Whether you choose to participate or not, it will not affect your treatment in our hospital. You have every right to withdraw at any stage in the research process.
Procedures and Protocol
The objective of the study is to correlate the clinical findings in a patient suspected with carcinoma breast with the occurrence of ER ,PR & HER2/nue in a core needle biopsy or post surgical histopathology specimen .
Written informed consent will be obtained from the patients agreeing to participate in the study.
Duration OCTOBER 2013 to OCTOBER 2015
Benefits
Personally you will be benefited directly from the research by helping the oncologist choose the further modality of treatment to proceed with for the patient. By taking part in this research, you will be helping the scientific world to learn more about the role of hormone receptors and HER2/nue receptor in the assessment of breast carcinoma and its application in the field of surgery and oncology, which in turn will also benefit other patients with similar complaints. Thus, possibly assisting in the faster treatment and better prognosis for patients with carcinoma breast.