Introduction: Hypercalcemia is a common metabolic disorder in patients with malignant diseases; it is primarily associated with multiple myeloma and other hematological malignancy, but hypercalcemia is also found in advanced solid cancers, particularly squamous cell cancer as lung cancer, head and neck cancer, breast cancer, kidney and prostate cancer [1]. Frequent clinical manifestations of malignancy-related hypercalcemia are: nausea, vomiting, ileus, anorexia, dehydration, renal failure, muscle weakness, psychosis, lethargy, coma, and cardiac abnormalities as short QT interval and atrial or ventricular arrhythmia [2]. At least two main mechanisms can be responsible for hypercalcemia in these patients: humoral malignancy-associated hypercalcemia and local osteolytic hypercalcemia [3].

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%–98.8%) and 80.9% (74.6%–81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%–98.5%), and 90.9% (50.8%–98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8–14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%–100%) and 80.3% (70.7%–89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%–94.1%) and 73.6% (67.2%–79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

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In an XX female, one of the two X chromosomes has been inactivated during early embryonic life to achieve a compensation of X-linked gene products between males and females, leaving only one allele of X-linked genes functional. There are some X-linked genes escaping the X-inactivation, i.e., being expressed from both alleles. Escape from X-inactivation varies at different levels; some genes have both alleles active in some women but only one allele active in others, whereas some other genes have both alleles active in neoplastic tissue but only one allele active normally. The X-inactivation may be considered functionally equivalent to a loss of heterozygosity (LOH) for some genes, whereas escape from X-inactivation may be equivalent to functional gene amplification for others. The physiological LOH may make X-linked tumor suppressor genes lose their function more easily, compared with autosomal tumor suppressor genes, thus predisposing women to cancer formation more easily. Moreover, the human X chromosome contains many genes related to cancer or to sex and reproduction. All these properties of the X chromosome suggest that it may play more important roles than any autosomal chromosome in the development and progression of reproductive and urologic cancers.

Abstract3,3 ¶-Diindolylmethane (DIM) is a stable condensation product of indole-3-carbanol, a potential breast cancer chemoprevention agent. Human breast cancer cell lines were studied to better understand its mechanisms.In vitro experiments were done in MCF-7, T47D, BT-20 and BT-474 cells using MTT, ELISA, immunoblotting assays, reverse transcription-PCR, protein half-life, confocal microscopy, cell fractionation, and immunoprecipitation assays. We found that DIM inhibited the growth of all four breast cancer cell lines (IC 50 s, 25-56 Mmol/L).