Place of birth and risk of gallbladder cancer in India.

CONTEXT: Within India, the incidence of gallbladder cancer (GBC) is characterized by marked geographical variation; however, the reasons for these differences are unclear. AIMS: To evaluate the role of place of birth, length of residence, and effect of migration from high‑ to low‑risk region on GBC development. SETTINGS AND DESIGN: Population‑based cancer registries (PBCRs); case–control study. SUBJECTS AND METHODS: Data of PBCRs were used to demonstrate geographical variation in GBC incidence rates. A case–control study data examined the role of birth place, residence length, and effect of migration in etiology of GBC. STATISTICAL ANALYSIS: Rate ratios for different PBCRs were estimated using Chennai Cancer Registry as the reference population. Odds ratios (ORs) for developing GBC in a high‑risk region compared to a low‑risk region and associated 95% confidence interval (CI) were estimated through unconditional logistic regression models using case–control study. RESULTS: GBC shows marked variation in incidence with risk highest in Northeast regions and lowest in South India. OR of 4.82 (95% CI: 3.87–5.99) was observed for developing GBC for individuals born in a high‑risk region compared to those born in a low‑risk region after adjusting for confounders. A dose–response relationship with increased risk with increased length of residence in a high‑risk region was observed (OR lifetime 5.58 [95% CI: 4.42–7.05]; Ptrend ≤ 0.001). The risk persisted even if study participant migrated from high‑ to low‑risk region (OR = 1.36; 95% CI: 1.02–1.82). CONCLUSIONS: The present study signifies the importance of place of birth, length of stay, and effect of migration from high‑ to low‑risk region in the development of GBC. The data indicate role of environmental and genetic factors in etiology of disease.

Rural urban differences in breast cancer in India .

Context: Breast cancer incidence rates are high in developed countries and much lower in less developed countries including India. Aims: The aim of the following study is to compare breast cancer incidence rates in rural, urban and metro regions of India and to estimate risk of developing breast cancer associated with residence in a rural area. Settings and Design: Descriptive and analytical study design. Materials and Methods: We extracted age adjusted incidence rate from 26 population-based cancer registries and data from hospital-based case-control study to estimate rate and risk ratio for developing breast cancer in an urban region compared with a rural residence. Statistical Analysis: The rate ratios and 95% confidence interval (CI) for developing breast cancer in the urban and metro region compared with rural registry of Barshi were estimated. The odds ratio (OR) and 95% CI for developing breast cancer in women residing in a rural region was estimated by fitting unconditional logistic regression using hospital-based case-control study data. Average annual percentage change in most recent 15 years (1996-2010) for Barshi (rural), Aurangabad (urban), and Mumbai (metro) cancer registry was obtained by fitting a log-linear model using joint point regression. Results: Living first 20 years of life in a rural area reduces the risk of breast cancer (OR = 0.65, 95% CI: 0.56-0.76). Conclusions: The current study demonstrates that lifestyle operative in a rural area is protective against risk of developing breast cancer.

Pathological complete response in locally advanced breast cancer: Determinants and predictive significance.

Background. Neoadjuvant chemotherapy is now the standard approach for most large breast cancers including locally advanced cancers of the breast. The majority of patients respond satisfactorily to chemotherapy with effective downsizing of tumours to consider breast conservation surgery. Pathological complete response (pathCR) is known to be a strong predictor of good outcome; however, many factors are known to influence the extent of response to chemotherapy. It has been observed that smaller the tumour, better is the response achieved in contrast to larger and locally advanced tumours where only one-third may respond well enough to merit breast conservation. Various other clinical, biological and molecular factors are also being evaluated as effective predictors of chemosensitivity. Most of these are either not easily available for all patients in developing countries or are overtly expensive and not applicable for all patients. Methods. We evaluated the clinical and pathological predictors of response to chemotherapy in 1402 women with locally advanced breast cancer. Results. There was a higher rate of pathCR in smaller tumours, younger women and ER-negative as well as triple negative tumours. The presence of ductal carcinoma in situ (DCIS) and lymphatic and vascular invasion (LVI) were associated with lower pathCR. Conclusion. In the absence of ready availability of expensive molecular and genomic assays, clinical parameters and standard histopathological variables can also be useful indicators of response to neoadjuvant chemotherapy. Additionally, they can help identify those who could be eventually conserved or have a better outcome.

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India.

Background: This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. Materials and Methods: The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. Results: A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. Conclusions: The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

Low axillary sampling in clinically node-negative operable breast cancer.

Background. Targeted sentinel node biopsy has been extensively validated. It has been incorporated into standard guidelines for axillary prediction in women with clinically node-negative operable breast cancer. However, the high cost of the gamma probe and the need for radiocolloid have limited its widespread acceptance in developing countries. We aimed to validate low axillary sampling as a reliable alternative method to sentinel node biopsy in a developing country. Methods. An anatomically guided low axillary sampling removes the lower level I axillary fat with lymph nodes and the method was validated by completing axillary clearance in all women. Results. Three hundred fifty-five women with clinically node-negative operable breast cancer underwent validation of low axillary sampling, with lymph nodes identified in all of them. The median number of nodes identified in low axillary sampling was 5 with overall node-positivity of 32.1% (114 of 355). Ten of these 114 patients were wrongly identified as node-negative by the sampled lymph nodes, i.e. a false-negative rate of 8.8%. Further exploratory analysis showed that 6-node low axillary sampling gave an excellent false-negative rate of 1.5% with 95% sensitivity, which was comparable with the highly targeted sentinel node biopsy technique. Conclusions. With an overall false-negative rate of 8.8% with 5-node low axillary sampling, and even better falsenegative rate of 1.5% with 6-node low axillary sampling, axillary sampling is a low-cost technology, which is a reliable alternative to sentinel node biopsy for axillary nodal prediction in clinically node-negative breast cancer.

HLA alleles in pre-menopausal breast cancer patients from western India.

BACKGROUND & OBJECTIVES: Cytotoxic function of Natural Killer (NK) cells is regulated by the products of HLA class I genes. Associations between HLA alleles and risk for cancers have been suggested earlier. Several reports further emphasize the need to examine influence of HLA genotypes on risk for malignant disorders. Therefore, we undertook this study to assess the possibility of association of HLA-class I alleles in pre-menopausal breast cancer patients. METHODS: Eighty one pre-menopausal breast cancer patients and 160, age and ethnicity matched healthy women from western India were studied. Genotyping for HLA class I alleles and HLA-B*40 alleles (high resolution) was performed using genotyping kits from Genovision Inc., USA. RESULTS: Nearly two-fold higher frequency of HLA - B*40 (16%) was observed in patients compared to controls (O.R. = 2.2; 95% C.I.-1.15-4.34; P<0.02). High resolution typing for HLA-B*40 alleles revealed predominance of HLA-B*4006 allele in both the study groups. Two other important observations relate to lower frequency of HLA - B*08 in patients and homozygosity at HLA-Cw locus in significantly higher proportion of patients. INTERPRETATION & CONCLUSION: The nature of peptides presented by HLA-B*4006 may have implications for higher frequency of HLA-B*40 in breast cancer patients. Higher frequency of homozygosity at HLA-Cw alleles in patients suggests a role for killer immunoglobulin-like receptors (KIRs) in NK cell mediated immune surveillance. Results of this study provide directions to further analyse role of immunogenetic mechanisms governing innate and adaptive immune responses contributing to modulation of risk for breast cancer.

Validation of EORTC quality-of-life questionnaire in Indian women with operable breast cancer.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) module QLQ-C30 and the breast cancer-specific module BR-23 have been validated worldwide to assess the quality of life (QOL) in women with breast cancer. No such study has been published on Indian women using EORTC questionnaires. METHODS: QOL was assessed in relation to surgery, adjuvant chemotherapy, radiation therapy and hormone therapy in 299 Indian women with operable breast cancer (OBC) at the Breast Unit of Tata Memorial Hospital (TMH), Mumbai, from October 1998 to September 2001. The QLQ-C30 module was used to assess physical health, emotional, cognitive and social functioning, and the BR-23 module to assess breast cancer treatment-related symptoms. Assessment was done at 3 visits: visit 1 (after surgery); visit 2 (during adjuvant therapy) and visit 3 (on completion of adjuvant therapy). RESULTS: Of the 299 women at first visit, 274 (91.6%) completed the visit 2 questionnaire and 239 (80%) completed the visit 3 questionnaire. Only those women who filled the questionnaires at all 3 visits were included as 'valid visits' for analysis (193 of 299; 64.5%). The reliability and validity of the English and translated versions of the questionnaires were tested by Cronbach alpha (0.61-0.96) and item-scale correlation (0.63-0.93). Women with breast conservation treatment had a superior body image as compared to those with mastectomy (p <0.001). Physical, emotional and cognitive functions were not related to the type of surgery. Global QOL, physical, sexual and role functioning were found to deteriorate with chemotherapy (p < or = 0.01). Radiotherapy had only local adverse effects (p < 0.001 ), while hormone therapy had no adverse impact on QOL. CONCLUSION: QLQ-C30 and BR-23 questionnaires can be used reliably to assess QOL in Indian patients. The translated versions were found to be valid for further use in clinical trials on Indian women with breast cancer.

Timing of surgery during the menstrual cycle and prognosis of breast cancer.

There are conflicting reports on the differential effect of surgery performed during the two phases of the menstrual cycle, namely, follicular and luteal, and prognosis of operable breast cancer. A statistical meta-analysis of the published evidence suggests a modest survival benefit of 15+/-4% when the operation is performed during the luteal phase. Further research in this area might provide a novel avenue to understand the natural history of breast cancer. A spin off from these studies might be the understanding of the importance of events that occur at the time of surgery in determining long term prognosis.

Role of high speed biopsy gun in breast cancer diagnosis.

Preoperative diagnosis of histology and receptor status is important in management of breast cancer. Percutaneous automated core biopsy with biopsy gun (Gun biopsy) was done in fifty patients with palpable breast lump in whom fine needle aspiration cytology (FNAC) was either negative or not done In all patients adequate tissue for histology and receptor status studies was obtained forty-two patients had infiltrating duct carcinoma and eight patients had benign lesions on gun biopsy. There were no complications in this procedure. Twenty of the forty-two patients underwent mastectomy either per primum or after chemotherapy, had the diagnosis substantiated on histopathological examination Thirty-four samples were examined for receptor status and the specimen was found to be adequate and of good quality. We conclude that gun biopsy is a simple and safe procedure which is more sensitive and specific than FNAC.

Clinico-pathological features and prognosis of breast cancer in different religious communities in India.

A study of clinical and pathological features, patterns of relapse and prognosis of breast cancer in various religious communities--viz. Hindu, Muslim, Christian and Parsi--was undertaken among 4377 evaluable cases treated at Tata Memorial Hospital between 1965 and 1982. Of these 82.4 per cent were Hindus, 7.3 per cent Muslims, 7.4 percent Christians and 2.7 percent Parsis. The mean age at diagnosis was 55 years for Parsis which was 7 to 8 years older than that for the other communities. There were no remarkable differences in histological tumour type or grade; except that parsis had higher incidence of uncommon histological types, such as dust carcinoma in situ and colloid carcinoma, and had a slightly more favourable grade distribution. When classified according to the TNM system (UICC 1978), the Parsis had the most favourable stage at presentation followed by Christians, Hindus and Muslims in that order. This trend was highly statistically significant (p less than 0.001). Despite this significant differences between stage of disease at diagnosis, no differences in the overall 5-year survival was observed between the communities. This remained true even after matching for disease stage and menopausal status. Even the Parsis, in whom the disease was detected relatively early, failed to register a survival advantage. Much work need to be done with regard to early detection of Breast Cancer in India.