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Opinion statementIn the past decade, several endocrine treatment regimens have been developed for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer, including tamoxifen, aromatase inhibitors (AI), or a combination of these. The standard duration of adjuvant endocrine treatment has been 5 years for a long time. Nevertheless, the high number of recurrences occurring after 5 years suggested that extended endocrine therapy could further improve outcome, which led to the start of several randomized clinical trials investigating the effects of extended use of endocrine therapy. The extended duration of tamoxifen has been shown to improve disease-free survival and overall survival in the ATLAS and aTTom trials. However, in postmenopausal women, AIs have been shown to be more effective when compared with tamoxifen. Based hereon, it is recommended that adjuvant endocrine therapy in postmenopausal women with early breast cancer should include an AI. Recently, the DATA, IDEAL, and NSABP B42 trials showed that extended adjuvant endocrine therapy with AIs beyond 5 years in postmenopausal women with early breast cancer did reduce the occurrence of secondary breast tumors, but had no or only a small impact on distant metastasis free survival. Furthermore, toxicity of adjuvant AIs led to gradually decreasing compliance rates and long-term toxicities to non-breast cancer-related deaths. Therefore, we suggest considering extended adjuvant treatment only in women with high-risk early breast cancer who tolerate treatment well.

PurposeTo assess the incidence of chemotherapy-induced ovarian function failure (COFF) based on estradiol and follicle stimulating hormone (FSH) monitoring in premenopausal women with hormone-receptor positive breast cancer treated with second and third generation (neo-)adjuvant chemotherapy.ResultsWe identified 115 eligible women. Two years after start of chemotherapy, COFF was significantly more often present in women ≥ 40 years (85.6%) as compared to women < 40 years (8.7%). Only age was significantly associated with COFF two years after start of chemotherapy (HR 12.26; 95% CI 5.21–28.86). In 50% of the patients, premenopausal hormone levels were the first or only evidence of ovarian function recovery (OFR).Materials and MethodsWe included all premenopausal women with hormone-receptor positive breast cancer treated with anthracycline-based chemotherapy, with or without taxanes, in our university hospital in the Netherlands in the years 2005-2013. Patients were 3-monthly monitored for ovarian function. Cox proportional hazards model was used to determine the predictive impact of various parameters on the occurrence of COFF.ConclusionsAfter second- or third generation (neo-)adjuvant chemotherapy, COFF was still present in 8.7% of patients < 40 years after two years. FSH and estradiol monitoring may be relevant for those in whom ovarian function suppression is considered an additional effective endocrine treatment.

The risk of OFR during AI treatment in breast cancer patients with chemotherapy-induced ovarian function failure is relevant, even beyond 45 years. Furthermore, women experiencing OFR had statistically significant higher estradiol levels during AI treatment (before OFR) than those without, with potential consequences regarding efficacy.

Purpose We assessed the uptake of fertility preservation (FP), recovery of ovarian function (OFR) after chemotherapy, live birth after breast cancer, and breast cancer outcomes in women with early-stage breast cancer. Methods Women aged below 41 years and referred to our center for FP counseling between 2008 and 2015 were included. Data on patient and tumor characteristics, ovarian function, cryopreservation (embryo/oocyte) and transfer, live birth, and disease-free survival were collected. Kaplan-Meier analyses were performed for time-to-event analyses including competing risk analyses, and patients with versus without FP were compared using the logrank test. Results Of 118 counseled women with a median age of 31 years (range 19-40), 34 (29%) chose FP. Women who chose FP had less often children, more often a male partner and more often favorable tumor characteristics. The 5-year OFR rate was 92% for the total group of counseled patients. In total, 26 women gave birth. The 5-year live birth rate was 27% for the total group of counseled patients. Only three women applied for transfer of their cryopreserved embryo(s), in two combined with preimplantation genetic diagnosis (PGD) because of BRCA1-mutation carrier ship. The 5-year disease-free survival rate was 91% versus 88%, for patients with versus without FP (P = 0.42). Conclusions Remarkably, most women achieved OFR, probably related to the young age at diagnosis. Most pregnancies occurred spontaneously, two of three women applied for embryo transfer because of the opportunity to apply for PGD.

The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2–3 years of tamoxifen. This planned side‐study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate‐use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T‐scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6‐ and 3‐year group respectively (p = 0.18), during follow‐up. Only two patients (3‐year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6‐ and 3‐year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD‐change during anastrozole in the lumbar spine showed a T‐score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole‐use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation.

Capecitabine is an oral fluoropyrimidine used as adjuvant and palliative chemotherapy in patients with colorectal cancer. Diarrhea is a well-known side effect of capecitabine and 5-fluorouracil agents. We present a case with terminal ileitis as a rare adverse event of capecitabine treatment. Capecitabine-induced terminal ileitis is likely to be underreported. It should be considered more often as a cause of severe and atypical complaints of diarrhea during treatment with capecitabine or other 5-fluorouracil agents.

Purpose The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS.Conclusion No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.Keywords Breast cancer · Tamoxifen · Aromatase inhibitor · Bone health · Osteoporosis · Bisphosphonates · Survival · Bone metastases · Distant recurrence-free survival Part of these results were presented at the poster session of the 2018 San Antonio Breast Cancer Symposium, abstract number 810.