No abstract

Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all breast cancers and male malignancies. Despite recognized clinico-pathological and molecular differences to female breast cancer (FBC), the clinical management of MBC follows established FBC treatment strategies. Loss of function mutations in the DNA damage response genes BRCA1 and BRCA2, have been strongly implicated in the pathogenesis of MBC. While there have been extensive clinical advancements in other BRCA-related malignancies, including FBC, improvements in MBC remain stagnant. Here we present a review that highlights the lack of treatment evidence for BRCA-related MBC and the required national and global collaborative effort to address this unmet need. In doing so, we summarize the transformative clinical advancements with poly(ADP-ribose) polymerase (PARP) inhibitors in other BRCA-related cancers namely, FBC and prostate cancer.

Background: GSTP1 is one of the Glutathione-S-Transferases (GSTs) which suppress tumor genesis by detoxifying toxic carcinogens and reactive oxygen species (ROS). Prostate cancer is related to several mutations affecting the expression of GSTP1. A single nucleotide polymorphism (SNP: Ile105Val) in the GSTP1 gene results insignificant reduction in its anticancer activity. The current case control study was conducted to ascertain the risk of association of GSTP1polymorphism with risk of cancer prostate in an Eastern Indian population. Materials and Methods: During a study period of 2 years, DNA was isolated using the phenol chloroform extraction method from the blood of 225 histopathologically diagnosed prostate cancer patients and 120 matched controls. The GSTP1 polymorphism was assessed by PCR amplification of the gene followed by restriction digestion with Alw261 (a restriction enzyme derived from Acinetobactro lwoffi RFL26). Histopathological grading in the case group was performed using Gleason’s scores and International Society of Urological Pathology (ISUP) grading. Results: Comparison of the distribution of different GSTP1 alleles between the case and control groups was performed by chi square test and odds ratio analysis. A χ2 value of 18.56 suggested significantly higher number of G alleles in the case group. An odds ratio of 2.25 with a confidence interval of 1.52 to 3.34 for 95% CI showed that the G allele in GSTP1 gene were linked with greater risk of prostate cancer. Post hoc ANOVA and logistic regression suggested that cases having G alleles had more progressive form of diseases as evident from ISUP grades. Conclusion: From our study we can conclude that GSTP1 polymorphism is not only significantly associated with risk of prostate cancer but also with its severity in our Eastern Indian population. GSTP1 polymorphism should be considered as a prognostic indicator for prostate cancer patients along with planning for more aggressive management of the disease.

No abstract

Breast cancer prognosis and management for both men and women are reliant upon estrogen receptor alpha (ERα) and progesterone receptor (PR) expression to inform therapy. Previous studies have shown that there are sex-specific binding characteristics of ERα and PR in breast cancer and, counterintuitively, ERα expression is more common in male than female breast cancer. We hypothesized that these differences could have morphological manifestations that are undetectable to human observers but could be elucidated computationally. To investigate this, we trained attention-based multiple instance learning prediction models for ERα and PR using H&E-stained images of female breast cancer from the Cancer Genome Atlas (TCGA) (n = 1085), and deployed them on external female (n = 192) and male breast cancer images (n = 245). Both targets were predicted in the internal (AUROC for ERα prediction: 0.86 ± 0.02, p < 0.001; AUROC for PR prediction = 0.76 ± 0.03, p < 0.001) and external female cohorts (AUROC for ERα prediction: 0.78 ± 0.03, p < 0.001; AUROC for PR prediction = 0.80 ± 0.04, p < 0.001) but not the male cohort (AUROC for ERα prediction: 0.66 ± 0.14, p = 0.43; AUROC for PR prediction = 0.63 ± 0.04, p = 0.05). This suggests that subtle morphological differences invisible upon visual inspection may exist between the sexes, supporting previous immunohistochemical, genomic, and transcriptomic analyses.