Survival Benefit of Chemotherapy According to 21-Gene Recurrence Score in Young Women with Breast Cancer.

BACKGROUND: Initial trials evaluating Oncotype DX, reported as a recurrence score (RS) from 0 to 100, were not powered to evaluate overall survival, and premenopausal women were underrepresented. The purpose of this study was to explore the benefit of chemotherapy according to RS among younger women eligible for oncotype testing. METHODS: Women aged 40-50, diagnosed with HR-positive, HER2-negative breast cancer between 2010 and 2017 were selected from the National Cancer Database (NCBD). Patients were grouped by age, RS, nodal status, and chemotherapy receipt. Kaplan-Meier curves were used to compare unadjusted overall survival (OS) between the groups, and log-rank tests were used to test for a difference between groups. Cox proportional hazards models were used to examine the association between select factors and OS. RESULTS: A total of 15,422 patients met inclusion criteria, 45.3% of whom received chemotherapy. Median follow-up time was 66.4 (50.6-86.6) months. Patients who received chemotherapy were more likely to have higher-stage and higher-grade tumors, tumors that were PR-negative, and have higher RS (p < 0.001 for all). RS was prognostic for OS regardless of nodal status. After adjustment, chemotherapy was associated with a significant improvement in OS only in the pN1 RS 31-50 subgroup (p = 0.02). CONCLUSIONS: RS retains its prognostic value in younger patients with early stage HR-positive, HER2-negative breast cancer. Chemotherapy survival benefit was limited to patients aged 40-50 with pN1 disease and RS of 31-50. Therefore, chemotherapy decision-making should be especially preference-sensitive in women aged 40-50 with intermediate RS, where it may not provide a survival benefit for many women.

Metabolic effects of oral contraceptives containing 30 micrograms and 50 micrograms of oestrogen.

In Study A, biochemical data from 17 women who were not taking oral contraceptives were compared with those from women taking preparations which contained either 30 microgram of ethinyl oestradiol and 150 microgram of D-norgestrel (18 women) or 50 microgram of ethinyl oestradiol and 250 microgram of D-norgestrel (nine women). In Study B, biochemical data were collected from eight women before and during the first three or four months therapy with preparations containing 30 microgram of ethinyl oestradiol and 150 microgram of D-norgestrel. The two oral contraceptive dosage forms studied produced qualitatively and quantitatively similar metabolic changes. Both caused an increase in serum concentration of triglycerides (30% to 33%), beta-lipoproteins (27% to 29%) and ceruloplasmin (75% to 90%), and a decrease in serum levels of antithrombin III (22% to 29%) and ascorbic acid (30% to 42%). Serum cholesterol and phospholipid concentrations were unchanged. However, the proportion of serum cholesterol carried by alpha-lipoproteins (high density lipoproteins) decreased, while that carried by beta-lipoproteins (low density and very low density lipoproteins) increased. The former change is in the same direction, but much smaller than that observed in coronary heart disease.

PIP: 2 studies, A and B, were conducted to determine the metabolic effects of oral contraceptives (OCs). The subjects were healthy nonsmokers (17 to 27 years old, 1.52 m. to 1.75 m. in height, and 50 kg. to 60 kg. in weight) who were not undergoing any therapy. Controls did not have any previous history of hormonal therapy. In Study A, biochemical data from 17 women who were not on OCs were compared with those of women taking pills containing either 30 ug of ethinyl estradiol (EE) and 150 ug of D. norgestrel (18 women) or 50 ug. of EE and 250 ug. of D. norgestrel (9 women). In Study B, 8 women were studied before and during 3 to 4 cycles of low-dosed OC therapy (30 ug. of EE and 150 ug. of D. norgestrel). In both studies, the 2 oral contraceptive dosage forms had similar metabolic quantitative and qualitative changes: both resulted in an increase in serum concentration of triglycerides (30 to 33%), B-lipoproteins (27 to 29%), and ceruloplasmin (75 to 90%), and a decrease in serum levels of antithrombin 3 (22 to 29%) and ascorbic acid (30 to 42%). Serum cholesterol and phospholipid concentration did not change. The proportion of serum cholesterol carried by a-lipoproteins (high density lipoproteins) did decrease (the change is much smaller than that seen in coronary heart disease) while that carried by B-lipoproteins (or low density and very low density lipoproteins) increased. A significant negative correlation was observed between serum concentrations of ascorbic acid and cholesterol; this is interesting as clinical and experimental evidence suggests that latent ascorbic acid deficiency leads to hypercholesteroleamia, while ascorbic acid supplements reduce plasma cholesterol levels. As 500 mg. daily of ascorbic acid supplements supposedly help maintain normal ascorbic acid levels in blood during OC use, they should perhaps be prescribed to pill users in this study.