COVID-19 risk in breast cancer patients receiving CDK4/6 inhibitors: literature data and a monocentric experience.

Substantial changes in the management of cancer patients have been required worldwide in response to the COVID-19 pandemic. Beyond the due details on the primitive cancer site and setting at diagnosis, these latter adaptions are most commonly exemplified by a significant reduction in the screening of asymptomatic subjects, delays in elective surgery and radiotherapy for primary tumors, and dose reductions and/or delays in systemic therapy administration. Advanced breast cancer patients with hormonal receptor positive, HER2 negative tumors are usually treated with endocrine therapy combined with CDK 4/6 inhibitors as first- and second-line treatment. During the pandemic, experts' recommendations have suggested the omission or delay of CDK 4/6 inhibitors delivery, or a careful evaluation of their real need due to the hypothesized increased risk of SARS-Cov-2 infection and disease possibly related to neutropenia. The inherent literature is sparse and inconsistent. We herein present data on the use of CDK 4/6 inhibitors during the pandemic. The evidence reported punctually reflects the experience matured at our Institution, a comprehensive cancer centre, on the topic of interest.

Anthropometric, metabolic and molecular determinants of human epidermal growth factor receptor 2 expression in luminal B breast cancer.

Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting glucose (

Unusual long-lasting cutaneous complete response to lapatinib and capecitabine in a heavily pretreated HER2-positive plurimetastatic breast cancer patient.

Lapatinib, in combination with capecitabine, has shown clinical activity in both first-line and refractory disease in patients with HER2-positive advanced breast cancer. Herein we describe the case of a plurimetastatic, heavily pretreated, HER2-positive breast cancer patient who experienced multiple cutaneous metastases successfully treated with lapatinib and capecitabine. An early complete response was obtained on all skin lesions, and no evidence of disease progression at other metastatic sites was observed for 22 months. The treatment was well tolerated, without dose-reductions or delays. In advanced breast cancer patients with skin metastases overexpressing HER2, previously treated with anthracyclines, taxanes and trastuzumab, lapatinib and capecitabine may represent a very active, safe and well-tolerated treatment option.

Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer.

The role of aromatase inhibitors combined with gonadotropin-releasing hormone analog in metastatic male breast cancer patients remains unknown. In this retrospective study we evaluated the activity of letrozole combined with a gonadotropin-releasing hormone analog as a first- or second-line therapy for metastatic male breast cancer patients. 19 men entered the study. We did not observe any grade 3 or 4 adverse events. 2 patients (10.5 %) had complete response, 7 patients (36.8 %) experienced a partial response, 7 patients (36.8 %) had stable disease lasting ≥ 6 months, and 3 patients (15.8 %) had progressive disease. Overall, the disease control rate was 84.2 %. Median progression-free survival was 12.5 months (95 % CI 8.2-16.9), median overall survival was 35.8 months (95 % CI 24.4-49.2), 1- and 2-year survival rates were 89.5 and 67 %, respectively. Interestingly, 3 out of 4 patients treated with the combination following disease progression while on aromatase inhibitor monotherapy confirmed or improved the best overall response observed in the first-line setting. The combination of letrozole and gonadotropin-releasing hormone analog is effective and safe in hormone-receptor positive, metastatic male breast cancer patients.

Vitamin D supplementation and breast cancer prevention: a systematic review and meta-analysis of randomized clinical trials.

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the "Related Article" feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I(2) test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74-1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23-1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54-1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.

Equol status modifies the association of soy intake and mammographic density in a sample of postmenopausal women.

Only 30% to 50% of people produce the daidzein-metabolite equol after eating soy. We conducted a cross-sectional study of the associations between equol status, intake of soy foods, and mammographic density in a sample of postmenopausal women recruited at a radiology clinic near Buffalo, New York. Participants were 48 to 82 years old, had no history of cancer or breast reduction/augmentation, and no recent use of antibiotics or hormones. Percent density was measured by computer-assisted analysis of digitized images of craniocaudal films. Equol status was assessed using a soy-challenge protocol and usual soy intake by questionnaire. General linear models were used to assess independent and joint effects of equol status and intake of soy on multivariate adjusted percent density (covariates included age, body mass index, parity, age at first birth, and ever use of combined hormone therapy). Of 325 enrolled, 232 (71%) participants completed study assessments and are included in the present analysis. Mean percent density was 34% (+/-18%). Seventy-five (30%) participants were producers of equol. Forty-three (19%) participants reported regularly eating >1 soy food or supplement/wk. There were no significant independent associations of equol status or soy intake with percent density, but the interaction between these factors was significant (P < 0.01). Among equol producers, those with weekly soy intake had lower percent density (30.7% in weekly consumers of soy versus 38.9% in others; P = 0.08); among nonproducers, weekly soy intake was associated with higher percent density (37.5% in weekly soy consumers versus 30.7% in others; P = 0.03). Results suggest that equol producers and nonproducers may experience different effects of dietary soy on breast tissue.

Erythrocyte membrane phospholipid composition as a biomarker of dietary fat.

BACKGROUND/AIMS: In a cross-sectional study, we investigated the relationship between erythrocyte membrane phospholipid fatty acid composition and dietary fat; we also investigated roles of menopausal status, age, body mass index (BMI) and waist-to-hip ratio (WHR) in interindividual variation of the biomarker. METHODS: Study participants were 204 women, aged 39-65 years, drawn from the ORDET cohort and selected as controls in a study of breast cancer. Membrane composition was assessed using capillary gas chromatography. Dietary fat composition was evaluated using a food frequency questionnaire. RESULTS: In pre- and postmenopausal women, erythrocyte membrane phospholipid levels of linoleic acid, oleic acid, and mono-unsaturated fatty acids were significantly associated with corresponding dietary measures (partial correlation coefficients: 0.23 and 0.39; 0.45 and 0.47; 0.40 and 0.48; respectively, in pre- and postmenopausal women). Among postmenopausal women, membrane poly-unsaturated fatty acids were correlated with the corresponding dietary measure (r=0.39, p<0.001). Membrane eicosapentanoic and docosahexanoic acid levels were significantly correlated with intake of fish/shell fish : r=0.21 and r=0.43 (premenopausal), and r=0.41 and r=0.44 (postmenopausal). Age, BMI and WHR had independent effects on membrane lipid composition. Age was associated with delta-6 desaturase activity in postmenopausal women (r=0.25, p<0.05). BMI was negatively associated with delta-9 desaturase activity in both pre- and postmenopausal women (r=-0.29, p=0.01 and r=-0.22, p<0.01, respectively). WHR was negatively associated with delta-5 desaturase activity in pre-menopausal women (r=-024, p<0.05). CONCLUSIONS: Erythrocyte membrane levels of some specific fatty acids can be used as biomarkers of these fatty acids as proportions of dietary fat.