Download carcinoma breast - Rajiv Gandhi University of Health Sciences

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
NAME OF THE
Dr. ABHISHEK .S. HEBLIKAR
CANDIDATE AND
DEPARTMENT OF GENERAL SURGERY
ADDRESS
SDM COLLEGE OF MEDICAL SCIENCES &
HOSPITAL
DHARWAD
2.
NAME OF THE
SHRI DHARMASTHALA
INSTITUTION
MANJUNATHESHWARA COLLEGE OF
MEDICAL SCIENCES & HOSPITAL
DHARWAD
3.
COURSE OF STUDY
M.S. (GENERAL SURGERY)
AND SUBJECT
4.
DATE OF JOINING THE
6 JUNE 2013
COURSE
5.
TITLE OF TOPIC
“RESPONSE TO NEO ADJUVANT
CHEMOTHERAPY IN CARCINOMA
BREAST "
6.
BRIEF RESUME OF THE INTEDED WORK:
6.1 Need for the Study
 Breast cancer is the second most common cancer close on the heels of the
cervical cancer in Indian women with an incidence rate of about 20 per
1,00,000..
 Breast cancer is no more considered a local disease; so the paradigm has
shifted from only locoregional control to systemic therapy.
 Most of the patients in our country, because of ignorance and lack of
awareness, present to us surgeons at fairly advanced stage. These locally
advanced cases cannot be treated with just locoregional management as
early relapse and poor survival is certain if these patients don‘t get systemic
therapy.
 Breast cancer is an extremely heterogeneous disease caused by interactions
of both inherited and environmental risk factors that lead to progressive
accumulation of genetic and epigenetic changes in breast cancer cells.
 The existence of certain risk factors (e.g., age, obesity, alcohol intake,
lifetime estrogen exposure, and mammographic density), a family history
of breast cancer remains the strongest risk factor for the disease. Familial
forms comprise approximately 20% of all breast cancers and appear to
have a distinctive pathogenesis dependent on the particular susceptibility
gene involved.
 Early diagnosis and treatment of the breast cancer provides better results,
neoadjuvant chemotherapy helps in reducing the tumour load and also
provides systemic therapy. Neoadjuvant chemotherapy is followed in our
hospital for patients with carcinoma breast on regular basis, this study will
help us in assessing response of the cancer and provides better insight for
future treatment.
6.2 REVIEW OF LITERATURE
Neoadjuvant chemotherapy is considered the standard of care for the
management of locally advanced breast carcinoma
1
Although
Neoadjuvant chemotherapy has not been shown to provide a survival
advantage over adjuvant chemotherapy, it allows assessment of disease
response to a particular chemotherapy regimen2.
Biologic rationale for pre-operative adjuvant chemotherapy was derived
from the pre-clinical studies in animal models. It had been known that
growth kinetics of metastatic tumors change after surgical removal of the
primary lesion3 . The greatest effect of chemotherapy was observed when
it was administered prior to operation4 5. These observations led to a
hypothesis that early systemic chemotherapy prior to surgery might further
reduce the risk of metastasis.
6
The landmark trial in a clinical setting was the National Surgical
Adjuvant Breast and Bowel Project (NSABP) B-18 trial, which showed
pre-operative chemotherapy for operable breast cancer by doxorubicin
60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) was at least as effective
as post-operative adjuvant chemotherapy with the same regimen in terms
of disease-free and overall survival7 .
The results were consistent over a longer follow-up period and the result of
another large randomized trial conducted in Europe was also confirmatory8
A recent meta-analysis of pre-operative and post-operative chemotherapy
(partly including T4 disease) indicated that pre-operative chemotherapy was
equivalent to post-operative therapy in terms of survival and disease
progression 9. Thus the available clinical data has not demonstrated a
convincing difference in long-term outcome as hypothesized in pre-clinical
studies. However, a higher proportion of women were able to undergo breast
conservation surgery. In addition, because the extent of clinical and
pathological responses to pre-operative chemotherapy correlates with survival,
improved tumor response in this setting is expected to improve the overall
outcome.
Prediction of Response to Pre-operative Chemotherapy
The pre-operative setting is ideal to explore molecular predictors of
response to therapy. Various clinical and pathologic variables have been
studied. Among them, ER status, histologic grade and smaller tumor size
seem to be associated with the response to pre-operative chemotherapy
10
.
In previous retrospective studies, clinical and pathological responses to
pre-operative chemotherapy appear to be lower in invasive lobular
carcinoma (ILC) as compared to invasive ductal carcinoma (IDC), and
patients with ILC were more likely to receive mastectomy after initial
attempt for breast conservation 11 12.
In a biomarker study, ER expression, absence of HER2 and a decrease
in Ki67 correlated with good clinical responses subsequent to a preoperative chemoendocrine therapy 13.
Using clinical or pathological responses as surrogate endpoints of overall
survival, optimal systemic therapies have been investigated in preoperative settings in patients with early breast cancer. The general
consensus reached is that an anthracycline-containing doublet (doxorubicin
or epirubicin with cyclophosphamide) or triplet (doxorubicin or epirubicin
with cyclophosphamide and 5-fluorouracil) should be used as the initial
chemotherapy strategy for pre-operative chemotherapy 14 15
6.2 Objectives of the Study
General objective
To assess the response(pathological complete response) of carcinoma breast to
neo adjuvant chemotherapy
7
MATERIALS AND METHODS
STUDY PERIOD : 1 YEAR(2013 DEC- 2014DEC)
7.1 Source of Data
This study includes patients attending surgey opd and in patients with carcinoma
breast at SDM medical college Dharwad.
7.2 Method of Collecting Data
Study design : Prospective study design.
Sample size: All cases of carcinoma breast with in duration of study period
would be included in the sample size.
Inclusion criteria: Patients with LABC who underwent Neoadjuvant
chemotherapy in the Department of general surgery SDMCMSH followed by
during the above period. LABC defined as to include stages II B, IIIA, IIIB,
IIIC.
Exclusion criteria:
Patients unfit for chemotherapy.
Inflammatory carcinoma of the breast
Methodology:
After a complete history, a physical examination with evaluation of both
breasts and all surrounding lymph node-bearing areas. All tumors would
be described by the longest perpendicular diameters in cm, and the
presence of palpable axillary, supraclavicular and subclavicular nodes,
with exact measurements of their longest perpendicular diameters, should
be included. After the physical examination and bilateral mammogram, the
following additional tests are recommended: a biochemical profile,
including tests of liver and renal function, and calcium level; chest x-ray;
bone scans; radiographs of areas that appear to be abnormal on the bone
scan; computed tomography of the liver and an ultrasonography of the
breast and regional lymph nodes to precisely assess the tumor extent. After
the patients are fit for chemotherapy, they receive 4 cycles of FAC
chemotherapy with 21 days gap between each cycle of chemotherapy.
Following
4
cycles
of
FAC
(5
fluorouracil,
adriamycin
and
cyclophosphamide) chemotherapy patients undergo surgery(modified
radical mastectomy).
DEFINITIONS
 complete response (CR) when no breast tumor was
palpable
 Partial response (PR) when the reduction in the tumor
area was ≥ 50%
 Pathological response when histopathological report
showed no evidence of tumour in the specimen
 No change (NC) when the tumor area was reduced <
50% or increased < 25%.
 Progressive disease (PD) was recorded if the tumor
area increased ≥ 25%, or if a new lesion was detected
7.3 Does the study require any investigation / intervention to be conducted on
patients / humans / animals? If so, please describe briefly.
 TRUCUT BIOPSY
 USG ABDOMEN
 CHEST XRAY
 B/L MAMMOGRAM
 CT SCAN/MRI SCAN(IF BONE SCAN SHOWED UPTAKE)
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Yes (copy enclosed)
8.
LIST OF REFERENCES
1. Hortobagyi GN, Blumenschein GR, Spanos W, et al: Multimodal treatment of
loco regionally advanced breast cancer. Cancer 51:763-768, 1983
2. Cunningham JD, Weiss SE, Ahmed S, et al: The efficacy of Neoadjuvant
chemotherapy compared to postoperative therapy in the treatment of locally
advanced breast cancer. Cancer Invest 16:80-86, 1998
3. Gunduz N, Fisher B, Saffer EA. (1979) Effect of surgical removal on the
growth and kinetics of residual tumor. Cancer Res 39 3861–3865
4. Fisher B, Gunduz N, Saffer EA. (1983) Influence of the interval between
primary tumor removal and chemotherapy on kinetics and growth of metastases.
Cancer Res 43 1488–92.
5. Straus MJ, Sege V, Choi SC. (1975) The effect of surgery and pretreatment or
post-treatment adjuvant chemotherapy on primary tumor growth in an animal
model. J Surg Oncol 7 497–512
6. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al.
(1998) Effect of preoperative chemotherapy on the outcome of women with
operable breast cancer. J Clin Oncol 16 2672–85
7. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al.
(1998) Effect of preoperative chemotherapy on the outcome of women with
operable breast cancer. J Clin Oncol 16 2672–85
8. Van der Hage JA, van de Velde CJH, Julien JP, Tubiana-Hulin M,
Vandervelden C, Duchateau L. (2001) Preoperative chemotherapy in primary
operable breast cancer: results from the European Organization for Research and
Treatment of Cancer Trial 10902. J Clin Oncol 19 4224–37
9. Mauri D, Pavlidis N, Ioannidis JP. (2005) Neoadjuvant versus adjuvant
systemic treatment in breast cacer: a meta-analysis. J Natl Cancer Inst 97 188–97
10. Amat S, Penault-Llorca F, Cure H, Le Bouedec G, Achard JL, van Praagh I, et
al. (2002) Scarff–Bloom–Richardson (SBR) grading: a pleitropic marker of
chemosensitivity in invasive ductal breast carcinomas treated by neoadjuvant
chemotherapy. Int J Oncol 20 791–6
11. Cristofanilli M, Gonzalez-Angulo A, Sneige N, Kau SW, Broglio K, Theriault
RL, et al. (2005) Invasive lobular carcinoma classic type: Response to primary
chemotherapy and survival outcomes. J Clin Oncol 23 41–8
12. Cocquyt VF, Blondeel PN, Depypere HT, Praet MM, Sheelfhout VR, Silva
OE, et al. (2003) Different responses to preoperative chemotherapy for invasive
lobular and invasive ductal carcinoma. Eur J Surg Oncol 29 361–7
13. Chang J, Powles TJ, Allred DC, Ashley SE, Clark GM, Makris A, et al. (1999)
Biologic markers as predictors of clinical outcome from systemic therapy for
primary operable breast cancer. J Clin Oncol 17 3058–63
14. Schwartz GF and Hortobagyi GN. (2004) Proceedings of the consensus
conference on neoadjuvant chemotherapy in carcinoma of the breastApril 26–28,
2003Philadelphia, Pennsylvania. Cancer 100 pp. 2512–32.
15. Kaufmann M, von Minckwitz G, Smith R, Valero V, Gianni L, Eiermann W,
et al. (2003) International expert panel of the use of primary (preoperative)
systemic treatment on operable breast cancer: review and recommendations. J Clin
Oncol 21 2600–8
9.
Signature of the Candidate
:
10.
Remarks of the guide
:
 Feasible of SDMCMSH.
 This being practical but streamline of regimen required.
11
Name and Designation of
11.1
Guide
: Dr B.Srinivas Pai
Professor of Surgery
SDMCMSH
11.2
Signature
:
11.3
Co-Guide (if any)
:
11.4
Signature
:
11.5
Head of the Department
: Dr Mallikarjun Desai
Professor & HOD
Department of surgery
SDMCMSH
11.6
Signature
12.
:
12.1 Remarks of the Chairman &
Principal
12.2 Signature
:
:
PROFORMA
EVALUATION OF THE PATIENT:
 NAME
DOA:
 AGE
 HOSPITAL NO
 MARITAL STATUS
 MENSTRUAL STATUS
 COMPLAINTS:
 LUMP
 DURATION OF LUMP
 NIPPLE DISCHARGE
 PAIN
 OTHER SYMPTOMS
 PHYSICAL EXAMINATION
 SIZE OF LUMP
 NO. OF LUMPS
 SITE
 SKIN CHANGES:NIPPLE RETRACTION
 PEAU DE ORANGE
 ULCERATION
 SATELITE NODULES
 AXILLA:



IPSIATERAL
CONTRALLATERAL
SUPRACLAVICULAR
 SYSTEMIC EXAMINATION:
 ABDOMEN
 CHEST
 SKELETAL SYSTEM
 INVESTIGATION:
 TRUCUT BIOPSY
 USG ABDOMEN
 CHEST XRAY
 B/L MAMMOGRAM
 BONE SCAN
 CT SCAN/MRI SCAN(IF BONE SCAN SHOWED UPTAKE)
 NEOADJUVANT CHEMOTHERAPY
4 cycles of FAC followed by Surgery
 All HORMONE REPLACEMENT THERAPY:
 ER positive patients were administered tamoxifen.
 Physical examination, diagnostic mammography, and sonography after 2 cycles of
chemotherapy to assess response.

In Non responders NACT was abandoned and MRM was done