https://dash.harvard.edu/bitstream/handle/1/17820849/4511219.pdf?sequence=1

Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/253689/PMC4176449.pdf

Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017

http://hub.hku.hk/bitstream/10722/234033/1/content.pdf

Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

Bisphosphonates (BPs) are the most commonly used medications for osteoporosis. This ASBMR report provides guidance on BP therapy duration with a risk-benefit perspective. Two trials provided evidence for long-term BP use. In the Fracture Intervention Trial Long-term Extension (FLEX), postmenopausal women receiving alendronate for 10 years had fewer clinical vertebral fractures than those switched to placebo after 5 years. In the HORIZON extension, women who received 6 annual infusions of zoledronic acid had fewer morphometric vertebral fractures compared with those switched to placebo after 3 years. Low hip T-score, between -2 and -2.5 in FLEX and below -2.5 in HORIZON extension, predicted a beneficial response to continued therapy. Hence, the Task Force suggests that after 5 years of oral BP or 3 years of intravenous BP, reassessment of risk should be considered. In women at high risk, for example, older women, those with a low hip T-score or high fracture risk score, those with previous major osteoporotic fracture, or who fracture on therapy, continuation of treatment for up to 10 years (oral) or 6 years (intravenous), with periodic evaluation, should be considered. The risk of atypical femoral fracture, but not osteonecrosis of the jaw, clearly increases with BP therapy duration, but such rare events are outweighed by vertebral fracture risk reduction in high-risk patients. For women not at high fracture risk after 3 to 5 years of BP treatment, a drug holiday of 2 to 3 years can be considered. The suggested approach for long-term BP use is based on limited evidence, only for vertebral fracture reduction, in mostly white postmenopausal women, and does not replace the need for clinical judgment. It may be applicable to men and patients with glucocorticoid-induced osteoporosis, with some adaptations. It is unlikely that future trials will provide data for formulating definitive recommendations. © 2015 American Society for Bone and Mineral Research.

Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research.

Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12

Background: While extended adjuvant therapy with aromatase inhibitors (AI) after initial tamoxifen has been demonstrated to improve disease-free-survival (DFS) of postmenopausal patients with hormone-receptor positive breast cancer, the optimal duration of extended AI is unknown. Moreover, it remains unclear whether patients after AI in the first 5 years benefit similarly from extended adjuvant AI therapy as patients after Tamoxifen. Methods: From February 2004 to June 2010, 3484 women with postmenopausal stage I-III hormone-receptor positive early breast cancer were randomized in 71 centers in Austria to receive either 2 years or 5 years of additional Anastrozole (1 mg daily) as extended adjuvant therapy, after initial 5 years of adjuvant endocrine treatment. Eligible patients had to be recurrence-free at 60 months of initial adjuvant therapy with Tamoxifen (Tam) or AI or Tam→AI, and younger than 80 years of age. Stratification factors were tumor stage, nodal status, initial endocrine therapy, adjuvant chemotherapy, and quantitative hormone receptors. Patients were followed-up at least annually. Primary end point of ABCSG-16 was DFS, secondary end points included overall survival (OS), fractures, contralateral breast cancer, and toxicity. Results: As of June 30, 2016, the median follow-up of the 3468 patients included in the analysis of ABCSG-16 was 105.9 months (IQR 102.2-110.3 months) after randomization (i.e. approx. 14 years after diagnosis). Median patient age was 64 years, 2507 (72%) patients had tumors smaller than 2 cm, 2301 (66%) patients were node-negative, 674 (19%) patients had high-grade tumors, 2683 (77%) patients had tumors both ER and PR positive. 2764 (80%) patients were treated with breast conserving surgery. Before randomization into ABCSG-16, 1000 (29%) patients had undergone (neo)adjuvant chemotherapy, 1774 (51%) patients had received 5 years of Tamoxifen, whereas 1688 (49%) patients had received other (AI containing) regimens in the first five years. As of June 30, 2016, 757 DFS events have been recorded, 377 (22%) in the 2-year group, and 380 (22%) in the 5-year group. There was no significant difference in DFS (HR 0.997, 95%CI 0.86-1.15, log rank p=0.982), in OS, time to secondary carcinoma and time to contralateral breast cancer. With respect to drug adherence, 81.2% of patients in the 2-year arm were taking the study drug still at 2 years, and 80.1% at 2 years in the 5-year arm. At 5 years, 65.6% of patients in the 5-year arm were still on the assigned medication. Bone fractures were more frequent in the 5-year arm (i.e. years 3 to 5 after randomization: 6% vs 4 %, HR=1.405, 95%CI 1.03-1.91, p=0.029). Conclusion: After 5 years of adjuvant endocrine therapy (Tamoxifen or AI or Sequence), 2 additional years of Anastrozole are sufficient for extended adjuvant therapy – a further extension to 5 additional years did not yield additional outcome benefit but added toxicity. Support: AstraZeneca Citation Format: Gnant M, Steger G, Greil R, Fitzal F, Mlineritsch B, Manfreda D, Tausch C, Balic M, Dubsky P, Moik M, Thaler J, Egle D, Bjelic-Radisic V, Selim U, Exner R, Singer C, Melbinger-Zeinitzer E, Haslbauer F, Stoger H, Helfgott R, Sevelda P, Trapl H, Wette V, Solkner L, Jakesz R. A prospective randomized multi-center phase-III trial of additional 2 versus additional 5 years of anastrozole after initial 5 years of adjuvant endocrine therapy – results from 3,484 postmenopausal women in the ABCSG-16 trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-01.

Abstract GS3-01: A prospective randomized multi-center phase-III trial of additional 2 versus additional 5 years of anastrozole after initial 5 years of adjuvant endocrine therapy – results from 3,484 postmenopausal women in the ABCSG-16 trial

Efficacy of tamoxifen±aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial

/pdf/efficacy-of-tamoxifen-aminoglutethimide-in-normal-weight-and-37p51ussp0.pdf

U Selim

Papers

Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12

Abstract GS3-01: A prospective randomized multi-center phase-III trial of additional 2 versus additional 5 years of anastrozole after initial 5 years of adjuvant endocrine therapy – results from 3,484 postmenopausal women in the ABCSG-16 trial

Efficacy of tamoxifen±aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial