Correlation of the Geriatric Assessment with Overall Survival in Older Patients with Cancer.

AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS: This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS: Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION: The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.

Validation of PREDICT Version 2.2 in a Retrospective Cohort of Indian Women With Operable Breast Cancer.

PURPOSE: Online prediction models that use known prognostic factors in breast cancer (BC) are routinely used to assist in decisions for adjuvant therapy. PREDICT Version 2.2 (P2.2) is one such online tool, which uses tumor size, lymph node involvement, grade, age, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, and Ki67. We performed an external validation in a retrospective cohort of patients treated at a tertiary center in India. METHODS: Women with operable BC between 2008 and 2016 with nonmetastatic, T1-T2 invasive, and HER2 receptor-negative BC and with available 5-year overall survival (OS) data were selected. Median predicted 5-year OS rates were used to calculate predicted events for the whole cohort and subgroups. The chi-square test was used to evaluate the goodness of fit of the tool. RESULTS: Of 11,760 cases registered between 2008 and 2016, 2,783 (23.66%) eligible patients with a median age of 50 (26-70) years and a median pT size of 2.5 (0.1-5) cm, 2,037 (73.19%) with grade 3 tumors, 1,172 (42.11%) with node-positive disease, 817 (29.35%) with triple-negative breast cancer, and 1,966 (70.64%) with HR-positive BC were included in the analysis. The observed 5-year OS and predicted 5-year OS in the whole cohort were 94.8% and 90.00%, respectively, with an absolute difference of 4.8% (95% CI, 3.417 to 6.198, P < .001). The observed 5-year OS and predicted 5-year OS were also different in various subgroups. CONCLUSION: PREDICT version 2.2 overestimated the number of deaths, with lower predicted 5-year OS compared with the observed value, in this retrospective Indian cohort. The reasons for this discrepancy could be differing biologic characteristics and possible selection bias in our cohort. We recommend a prospective validation of PREDICT in Indian patients and advocate caution in its use until such validation is achieved.

Retrospective audit of the yield of internal mammary lymph node dissection and literature review in the management of breast cancer.

BACKGROUND: Treatment of lymph node basins is prognostic and therapeutic for axillary lymph nodes (ALN) as well as internal mammary lymph nodes (IMLNs) in breast cancer. IMLNs can be the first echelon node for the inner/central quadrants of the breast. We evaluated the yield of IMLN dissection (IMLND) mainly in patients with inner and central tumors. METHODS: IMLND was performed in 199 patients between 2000 and 2018, 127 of whom had tumors in the inner/ central quadrants. Clinico-pathological data were retrieved from Electronic Medical Records (EMR). RESULTS: The median age was 50 (range: 24-81). Primary surgery was performed in 82 (41.2%), while 117 (58.8%) were operated post-chemotherapy. Overall, 124/199 (62.3%) had nodes identified in the specimen, more often in primary (61/82, 74.4%) than post-chemotherapy settings (63/117, 53.8%) (P = 0.003). A median of 1 (average: 1.24, range: 0-7) lymph nodes was dissected, and 1 (average: 1.5, range: 1-4) was involved. IMLN was positive in 46/199 (23.1%) patients, not significantly different in primary (21/82, 25.6%) versus post-chemotherapy (25/117, 21.4%) settings (P = 0.545). IMLN was involved in 44.8% of patients with ≥4 involved ALN and 8.2% with uninvolved ALN (P < 0.001). In the absence of ALN involvement and <2cm pT size, 9% of patients had positive IMLN in inner/central quadrant tumors. In univariate analysis, ALN positivity (P < 0.001), pT size (P = 0.023), and grade (P = 0.041) in primary and ALN involvement (P = 0.011) in post-chemotherapy patients were associated with IMLN involvement. On logistic regression, tumor size (OR: 13.914, P = 0.017) and ALN involvement (OR: 11.400, P = 0.005) in primary surgery and ALN involvement (OR: 7.294, P = 0.003) in post-chemotherapy patients correlated with IMLN involvement. CONCLUSIONS: In inner/central quadrant tumors, IMLN is more likely involved with high ALN burden and tumor size >2 cm, whereas those with ≤2cm inner/central quadrant tumors and negative ALN have <10% probability of IMLN involvement.

Accuracy of Intraoperative Frozen Section Analysis of Lymph Nodes in Women Undergoing Axillary Sampling for Treatment of Breast Cancer: Single Institution Audit.

BACKGROUND: Axillary lymph node (LN) positivity is an important prognostic factor in breast cancer. Almost 30% clinically node negative (cN0) early breast cancers have positive nodes on pathology, wherein an axillary dissection is done as a second stage surgery. Intra operative frozen section (FS) potentially avoids redo surgery. MATERIALS AND METHODS: We performed a retrospective audit for the false negative rate of intraoperative FS, from 2014 to 2018. All cN0 women undergoing upfront surgery, who underwent low axillary sampling (LAS) with FS were included. RESULTS: Of 22,854 breast cancer cases, 2230 underwent LAS, of which 877 were node positive. Intraoperative FS was negative in 1423/2230 (63.81%) cases, of which 71/1423 (4.98%) were false negative, and came positive on final histopathology report (HPR). These 71 women had a median of 5 nodes (mean 4.85) dissected on FS (range 1-12) with a median 1 (mean 1.3) node positive (range 1-6) on HPR. The sensitivity of FS was 91.89% (95% CI, 89.89-93.62), with a negative predictive value of 95.01% (95% CI, 93.84-95.97), accuracy of 96.73% (95% CI, 95.90-97.43) and false negative rate 4.98%. On logistic regression analysis, micrometastasis (Odds ratio (OR) 7.76, 95% CI, 3.49-17.25, P < .001) lobular histology (OR 2.50, 95% CI, 1.007-6.223, P = .04) and nodes dissected (OR 1.18, 95% CI, 1.07-1.30, P = .001) were associated with higher false negative FS, and extra nodal extension (OR 0.32, 95% CI, 0.18-0.57, P ≤ .001) with lower false negative FS. CONCLUSION: The high concordance between intraoperative FS and definitive histology, suggests it's routine use for Sentinel lymph node/LAS LN can help avoid a second surgery.

Unique challenges and outcomes of young women with breast cancers from a tertiary care cancer centre in India.

BACKGROUND: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying. METHODS: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed. RESULTS: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients. CONCLUSION: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.

Trends in breast and cervical cancer in India under National Cancer Registry Programme: An Age-Period-Cohort analysis.

BACKGROUND: Trend analysis in cancer quantifies the incidence rate and explains the trend and pattern. Breast and cervical cancers are the two most common cancers among Indian women which contributed 39.4 % to the total cancer in India for the year 2020. This study aimed to report the time trends in cancer incidence of breast and cervical cancer using Age-Period-Cohort (APC) model from five Population Based Cancer Registries (PBCRs) in India for the period of 1985-2014. METHOD: Age-Period-Cohort model was fitted to five PBCRs of Bangalore, Chennai, Delhi, Bhopal and Barshi rural for breast and cervical cancer for 25-74 age-groups. The Estimated Annual Percent Change (EAPC) was calculated. Rate Ratio (RR) of cohort effects were estimated with a constraint of period slope to be zero (p = 0) since cohort has a stronger association with incidence than period. RESULT: A significant increase was noted in breast cancer in all PBCRs (EAPC, Range: Delhi, 1.2 % to Bangalore, 2.7 %) while significant decrease in cervical cancer (EAPC, Range: Bangalore -2.5 % to Chennai, -4.6 %) from all the PBCRs including Barshi rural during the period. RR estimates for breast cancer showed increasing trend whereas cervical cancer showed decreasing trend in successive birth cohorts across all five PBCRs. CONCLUSION: In both breast and cervical cancers, a significant age, cohort and period effect was noted in Bangalore, Chennai and Delhi. Despite period effect, the cohort effect was predominant and it may be attributed to the generational changes in risk factors among cancer breast and cervix.

Can We Avoid Axillary Lymph Node Dissection (ALND) in Patients with 1-2 Positive Sentinel/Low Axillary Lymph Nodes (SLN/LAS+) in the Indian Setting?

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Pregnancy associated breast cancer (PABC): Report from a gestational cancer registry from a tertiary cancer care centre, India.

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC. RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.

Transposition flap for the oncoplastic reconstruction of outer quadrant breast defects.

Plastic surgical principles are incorporated with breast conservation surgery (BCS) for cancer to improve aesthetic outcomes. In developing countries, average tumour size is larger at presentation resulting in larger resections often, including overlying skin. LD flap has been the workhorse of partial breast reconstruction. We present an easy and effective alternative to LD flap for carefully selected cases of outer quadrant breast tumours. We report 41 cases of local transposition flap from the lateral chest wall for oncoplastic restoration post BCS, performed between January 2016 and February 2020, at our institution. The median age was 49 years (28-63). Twenty-six patients underwent upfront surgery and 15 after neoadjuvant chemotherapy (NACT). The average pathological tumour size was 2.9 cm (median 2.7 and range 1.1-6) and 1.5 cm (median 1.8 and range 0-3.5) for upfront and post-NACT groups, respectively. The median volume of the resected specimen was 277.8 ml and 253.2 ml for upfront and post-NACT groups, respectively. Three patients (7.5%) had a microscopic positive margin requiring margin revision. Three (7.5%) patients had post-operative minor wound complications and were managed conservatively. At a median follow-up of 14 months (1-36), only 2/19 (10.5%) patients had clinical fat necrosis. Local transposition flap from the lateral chest wall based on dermal and subdermal plexus, carefully designed in selected patients, can be used effectively for the reconstruction of outer quadrant breast defects. It is easy to learn, offers good cosmetic outcome, avoids the morbidity and time of LD flap and saves LD flap for future use.

Does a less intensive surveillance protocol affect the survival of patients after treatment of a sarcoma of the limb? updated results of the randomized TOSS study.

AIMS: A single-centre prospective randomized trial was conducted to investigate whether a less intensive follow-up protocol would not be inferior to a conventional follow-up protocol, in terms of overall survival, in patients who have undergone surgery for sarcoma of the limb. Initial short-term results were published in 2014. PATIENTS AND METHODS: The primary objective was to show non-inferiority of a chest radiograph (CXR) group compared with a CT scan group, and of a less frequent (six-monthly) group than a more frequent (three-monthly) group, in two-by-two comparison. The primary outcome was overall survival and the secondary outcome was a recurrence-free survival. Five-year survival was compared between the CXR and CT scan groups and between the three-monthly and six-monthly groups. Of 500 patients who were enrolled, 476 were available for follow-up. Survival analyses were performed on a per-protocol basis (n = 412). RESULTS: The updated results recorded 12 (2.4%) local recurrences, 182 (36.8%) metastases, and 56 (11.3%) combined (local + metastases) recurrence at a median follow-up of 81 months (60 to 118). Of 68 local recurrences, 60 (88%) were identified by the patients themselves. The six-monthly regime (overall survival (OS) 54%, recurrence-free survival (RFS) 46%) did not lead to a worse survival and was not inferior to the three-monthly regime (OS 55%, RFS 47%) in terms of detecting recurrence. Although CT scans (OS 53%, RFS 54%) detected pulmonary metastasis earlier, it did not lead to a better survival compared with CXR (OS 56%, RFS 59%). CONCLUSION: The overall survival of patients who are treated for a sarcoma of the limb is not inferior to those followed up with a less intensive regimen than a more intensive protocol, in terms of frequency of visits and mode of imaging. CXR at six-monthly intervals and patient education about examination of the site of the surgery will detect most recurrences without deleterious effects on the eventual outcome. Cite this article: Bone Joint J 2018;100-B:262-8.

Predicting loco-regional recurrence risk in T1, T2 breast cancer with 1-3 positive axillary nodes postmastectomy: Development of a predictive nomogram.

BACKGROUND: Role of postmastectomy radiotherapy (PMRT) in early breast cancer with 1-3 positive axillary nodes is still controversial. Hence, there is a need to identify subgroup of patients who have sufficiently high risk of disease recurrence to benefit from PMRT. AIM: The aim is to evaluate clinical outcomes of patients postmastectomy having pathological T1-T2 tumors with 1-3 positive axillary lymph nodes (LNs) treated with adjuvant systemic therapy and develop a predictive nomogram. MATERIALS AND METHODS: Data collected retrospectively from eligible patients from 2005 to 2011. Kaplan-Meier survival analysis was used for all time-to-event analysis. Various known clinical and pathological risk factors were correlated with outcome using uni- and multi-variable analysis in SPSS version 21. All comparisons were two-tailed and P < 0.05 were considered statistically significant. The nomogram to predict the risk of loco-regional control (LRC) was developed using least absolute shrinkage and selection operator shrinkage model in hdnom.io software. RESULTS: 38/242 (15.7%) patients had recurrent disease at loco-regional (10 patients), distant sites (22 patients) and simultaneous loco-regional and distant sites (6 patients) at a median follow-up 59.5 (range 4-133) months. Five years estimate of LRC, distant disease-free survival (DFS), DFS, cause-specific survival and overall survival was 87.8%, 85.4%, 84.2%, 93.1%, and 91.5%, respectively. Pathological tumor size, margin status, LN ratio as continuous variables and grade and triple negative breast cancer status as categorical variables were the risk factors included in the model for building nomogram. CONCLUSION: The nomogram developed based on institutional data can be a valuable tool in guiding adjuvant PMRT depending on the risk of 5 years loco-regional recurrence.

Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor-positive metastatic breast cancer - A retrospective pilot analysis and viewpoint.

INTRODUCTION: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR) inhibitor, everolimus, in endocrine receptor (ER)-positive metastatic breast cancer (MBC) are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN) expression and correlating their expression with response and survival. MATERIALS AND METHODS: MBC patients who received everolimus with endocrine therapy (ET) after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. RESULTS: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6%) patients and retained in 2/13 patients (15.4%). mTOR activity was absent in four patients (30.7%), weak in six patients (46.1%), and moderate in 3 patients (23.2%). Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months) than those with weak and moderate activity, respectively (P = 0.043). There was no correlation between loss of PTEN expression and PFS. CONCLUSIONS: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study.

Taxane Combination Chemotherapy in Breast Cancer: Experience from a Tertiary Cancer Centre in India.

AIMS: Docetaxel, Doxorubicin, Cyclophosphamide (TAC) is an intensive chemotherapy regimen; however, being highly myelosuppressive, its usage is limited in developing countries and hence merits exploration for feasibility and efficacy. MATERIALS AND METHODS: This was a retrospective audit of medical records of breast cancer patients receiving TAC chemotherapy) from 2004 to 2008. Demographic details, toxicity, and outcome analysis were carried out. RESULTS: A total of 133 patients (126 in [neo] adjuvant and 7 in metastatic setting) received TAC chemotherapy. The median age was 45 (21-67) years; 31% had coexisting diabetes and 12% hypertension. The delivered dose intensity was 94%. Discontinuation rate was 21/133 (15.8%) and the most common reason was hematological toxicity. There were 43 (32%) cases of febrile neutropenia and 2 (1.5%) Grade III thrombocytopenia with 3 (2%) toxic deaths. Grade III gastrointestinal toxicity (diarrhea) occurred in 35 (26%) and cardiac toxicity (congestive cardiac failure) in 2 (1.5%) patients. On univariate analysis, none of the variables (baseline serum albumin, hemoglobin, disease stage, or age) was found significant for chemotoxicity. At a median follow-up of 27 months (0.13-71.30 months), the estimated median disease-free survival (DFS) was 52 months in locally advanced group; however, the early breast cancer cohort has not reached to median DFS. CONCLUSIONS: TAC is an effective regimen but has significant toxicity despite the use of primary prophylactic Granulocyte Colony-Stimulating-Factor (G-GSF), including a small possibility of death. It can be considered "practically feasible" regimen in the adjuvant setting in carefully selected, fit patients.

Central obesity increases risk of breast cancer irrespective of menopausal and hormonal receptor status in women of South Asian Ethnicity.

BACKGROUND: Current evidence suggests that the relationship between obesity and breast cancer (BC) risk may vary between ethnic groups. METHODS: A total of 1633 BC cases and 1504 controls were enrolled in hospital-based case-control study in Mumbai, India, from 2009 to 2013. Along with detailed questionnaire, we collected anthropometric measurements on all participants. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence interval (CI) for BC risk associated with anthropometry measurements, stratified on tumour subtype and menopausal status. RESULTS: Waist-to-hip ratio (WHR) of ≥0.95 was strongly associated with risk of BC compared to WHR ≤0.84 in both premenopausal (OR = 4.3; 95% CI: 2.9-6.3) and postmenopausal women (OR = 3.4; 95% CI: 2.4-4.8) after adjustment for body mass index (BMI). Premenopausal women with a BMI ≥30 were at lower risk compared to women with normal BMI (OR = 0.5; 95% CI: 0.4-0.8). A similar protective effect was observed in women who were postmenopausal for <10 years (OR = 0.6; 95% CI: 0.4-0.9) but not in women who were postmenopausal for ≥10 years (OR = 1.8; 95% CI: 1.1-3.3). Overweight and obese women (BMI: 25-29.9 and ≥ 30 kg/m(2), respectively) were at increased BC risk irrespective of menopausal status if their WHR ≥0.95. Central obesity (measured in terms of WC and WHR) increased the risk of both premenopausal and postmenopausal BCs irrespective of hormone receptor (HR) status. CONCLUSIONS: Central obesity appears to be a key risk factor for BC irrespective of menopausal or HR status in Indian women with no history of hormone replacement therapy.

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.

A grid matrix-based Raman spectroscopic method to characterize different cell milieu in biopsied axillary sentinel lymph nodes of breast cancer patients.

Raman spectroscopy which is based upon inelastic scattering of photons has a potential to emerge as a noninvasive bedside in vivo or ex vivo molecular diagnostic tool. There is a need to improve the sensitivity and predictability of Raman spectroscopy. We developed a grid matrix-based tissue mapping protocol to acquire cellular-specific spectra that also involved digital microscopy for localizing malignant and lymphocytic cells in sentinel lymph node biopsy sample. Biosignals acquired from specific cellular milieu were subjected to an advanced supervised analytical method, i.e., cross-correlation and peak-to-peak ratio in addition to PCA and PC-LDA. We observed decreased spectral intensity as well as shift in the spectral peaks of amides and lipid bands in the completely metastatic (cancer cells) lymph nodes with high cellular density. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to create an automated smart diagnostic tool for bench side screening of sampled lymph nodes. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to develop an automated smart diagnostic tool for bench side screening of sampled lymph nodes supported by ongoing global research in developing better technology and signal and big data processing algorithms.