Androgen receptor status predicts response to chemotherapy, not risk of breast cancer in Indian women

<p>Abstract</p> <p>Background</p> <p>Considerably little is known about the biological role and clinical significance of androgen receptor expression in breast cancer. The objectives of this study were to characterize <it>AR</it>-CAG repeat genotypes in a cohort of women with breast cancer and to determine the influence of AR on response to neoadjuvant chemotherapy and clinical outcome.</p> <p>Materials and methods</p> <p>Genotyping of the <it>AR </it>CAG repeat region was done on 70 patients and 80 healthy aged- matched female controls. To assess response to NACT, tissue samples from 30 LABC cases were evaluated quantitatively by real time for AR mRNA expression. The clinical response was correlated with both the pre and post chemotherapy AR expression. The CAG alleles did not show differences between cases and controls when the mean of short, long and average length of both CAG alleles was considered. However, analysis when done defining short allele as CAGn < 20 (AR1) and the long as CAGn ≥ 20 (AR2), risk was found associated with AR2 allele with marginal significance (P = 0.09). Stratification by age of onset, FH, stage, grade ER and AR status failed to reveal any association with breast cancer risk. Genotype carriers with ≥20 CAGn showed decrease of AR mRNA expression although significance could not be established (P = 0.47). Tumours in responders had the higher AR mRNA expression levels in pre neo-adjuvant chemotherapy condition (p < 0.02) which got reduced after neoadjuvant chemotherapy and the difference was found to be significant (P = 0.014).</p> <p>Conclusions</p> <p>Although, expansion of the CAGn in the <it>AR </it>gene doesn't show any major effect on breast cancer risk, patients with positive AR expression, pre neoadjuvant chemotherapy, were found to be good responders and a decrease in mRNA level of <it>AR </it>gene related to the chemotherapy-induced apoptosis could serve as an important independent predictor of response to NACT.</p

Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India

BACKGROUND: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls. METHOD: Cases were selected with regard to early onset disease (≤40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants. RESULTS: In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation. CONCLUSION: BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients

Impact of COVID-19 on quality of care indicators in patients of carcinoma cervix treated with definitive radiotherapy: A cross-sectional study

Introduction The COVID-19 pandemic has affected cancer care worldwide. We audited adherence to 19 predefined quality indicators (QI) of treatment in patients with carcinoma cervix in our institute. Methods Patients with carcinoma cervix treated with curative intent radical radiotherapy were eligible for this study. Patients who started treatment between 24 March 2019 and 24 March 2021 were evaluated. We divided participants into two groups, the pre pandemic period between 24 March 2019 and 23 March 2020, and the period of pandemic from 24 March 2020 - 24 March 2021. Adherence to 19 predefined QI was evaluated for each patient’s treatment course. Multivariable analysis of adherence to QI was performed using proportional odds regression. Results 154 patients underwent treatment, of whom 83 (53.9%) received treatment during the pandemic. 17 patients had COVID-19 infection before or during treatment. Adherence to QI decreased during the pandemic, primarily driven by delays in the start and delivery of treatment. The median number of QI adhered to in the pre pandemic period was 17 (IQR: 16 - 17.5) versus 17 during the pandemic (IQR: 16 - 17). Multivariable analysis showed that treatment during the pandemic period was associated with a lower adherence to QI (Odds ratio 3.30, 95% confidence intervals 1.70 - 6.50). Conclusions The COVID-19 pandemic was associated with reduced adherence to QI. Treatment delivery was affected not only by COVID-19 infection, but also logistic challenges due to restrictions related to the pandemic