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Purpose: POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer) is a prospective clinical trial assessing safety and pregnancy outcomes in premenopausal hormone receptor-positive breast cancer survivors (age ≤42) who interrupt endocrine therapy (ET) to attempt pregnancy. We sought to assess interest in this study and perspectives on fertility preservation (FP) among United States medical oncologists who had previously enrolled women at their institutions on select premenopausal endocrine studies. Methods: From August 2015 to December 2015, 301 investigators were invited to complete a web-based survey on behalf of their institution. We assessed FP practices and attitudes, barriers to discussing FP, and willingness to open/enroll women on POSITIVE. Results: Of 93 respondents (31%), most were affiliated with an National Cancer Institute (NCI)-designated comprehensive cancer center (44%). Almost all said they usually or always discussed the issue of future fertility with patients (98%) and referred patients with fertility questions to specialists (97%). Over half of respondents cited discomfort with recommending women to stop ET, as well as perceived patient concern regarding ET interruption, as factors seen as influencing POSITIVE enrollment; however, 84% were willing to recommend trial participation for selected patients. Conclusions: Most providers reported discussing fertility with their young patients, indicating awareness of FP guidelines for cancer patients. While most oncologists said that they would be willing to recommend POSITIVE, many also expressed discomfort in endorsing women to stop ET temporarily, underscoring the need for prospective data regarding the safety of ET interruption. High willingness to recommend POSITIVE suggests the potential for successful accrual to this study, which addresses a critical issue for young breast cancer survivors. [ABSTRACT FROM AUTHOR]

Optimal adjuvant endocrine therapy for premenopausal women with hormone-receptor positive breast cancer has long been debated. In particular, the role of ovarian function suppression in addition to standard tamoxifen divided oncologists worldwide, and more recently, the role of aromatase inhibitors as an alternative to tamoxifen in the setting of ovarian suppression became a key question. In 2014, the long awaited results of the International Breast Cancer Study Group (IBCSG) led randomized, phase 3 trials, Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT), provided additional evidence to inform the discussion. The interpretation of the SOFT and TEXT trial data can facilitate better selection of appropriate endocrine therapy according to individual disease characteristics, recognizing the complexity of the puzzle, which is still not complete. [ABSTRACT FROM AUTHOR]

The optimal endocrine therapy for premenopausal women with early and advanced breast cancer still remains an important and controversial issue. For over 30 years, tamoxifen has been the gold standard in the adjuvant setting. New therapeutic options, such as the addition of ovarian function suppression to oral endocrine therapy (either tamoxifen or aromatase inhibitors), can improve outcomes over tamoxifen alone in well-selected patients. Treatment duration has also been revisited, and extended therapy is becoming a new standard of care, especially in high-risk patients. Endocrine therapy for advanced disease still represents a challenge and a research priority. New drugs and combinations able to overcome endocrine resistance are at the horizon, and their role in premenopausal women should be better elucidated. Side effects and quality of life (including family planning considerations) play an important role in treatment selection and in the patients' treatment adherence and should always be discussed before start of treatment. The paper will specifically focus on how to integrate all new treatment options in the current armamentarium of endocrine therapy of premenopausal women, with the aim of best fine-tuning treatment selections according to the individual risk/benefit evaluation. [ABSTRACT FROM AUTHOR]

Managing estrogen receptor-positive breast cancer in young women (<40 years) requires a multidisciplinary/personalized approach, covering both clinical and psychosocial aspects. Five years of tamoxifen has been the standard adjuvant endocrine therapy for many years. Recent data from the adjuvant randomized trials TEXT-SOFT show that the aromatase inhibitor exemestane plus ovarian suppression significantly reduces recurrences as compared with tamoxifen plus ovarian suppression. The ATLAS and aTToM trials represent the first evidence of a beneficial effect of extended endocrine therapy with tamoxifen in premenopausal women. Outside of a clinical trial, no data support neoadjuvant endocrine therapy in young women. In the metastatic setting, tamoxifen or aromatase inhibitors, both with ovarian suppression/ablation, should be the preferred choice, unless rapid tumor shrinkage is needed. No data are available with fulvestrant in young patients. [ABSTRACT FROM AUTHOR]

Managing estrogen receptor-positive breast cancer in young women (<40 years) requires a multidisciplinary/personalized approach, covering both clinical and psychosocial aspects. Five years of tamoxifen has been the standard adjuvant endocrine therapy for many years. Recent data from the adjuvant randomized trials TEXT-SOFT show that the aromatase inhibitor exemestane plus ovarian suppression significantly reduces recurrences as compared with tamoxifen plus ovarian suppression. The ATLAS and aTToM trials represent the first evidence of a beneficial effect of extended endocrine therapy with tamoxifen in premenopausal women. Outside of a clinical trial, no data support neoadjuvant endocrine therapy in young women. In the metastatic setting, tamoxifen or aromatase inhibitors, both with ovarian suppression/ablation, should be the preferred choice, unless rapid tumor shrinkage is needed. No data are available with fulvestrant in young patients. [ABSTRACT FROM AUTHOR]

Abstract: Treatment of metastatic breast cancer has substantially changed in the last decades. Availability of new cytotoxics and targeted therapies as well as changes in treatment philosophy and strategy have all contributed to a significant improvement in both survival and patients’ quality of life. The multidisciplinary approach, personalised treatments based on tumour characteristics, patient’s and disease history, as well as re-definition of treatment goals, aiming at the lowest possible impact on patients’ life by replacing aggressive multidrug chemotherapy with single-agent cytotoxic treatment or endocrine±targeted therapies, have all been the bases of the new treatment paradigm. More recently the development of the international advanced breast cancer (ABC) consensus guidelines have further contributed to this improvement. This review will focus on the major achievements and challenges in the different tumour subtypes and sites, with a focus on future research topics and trends. [Copyright &y& Elsevier]

Abstract: Adjuvant treatment with aromatase inhibitors (AIs) improves outcomes in postmenopausal women with hormone-sensitive early breast cancer compared with tamoxifen. However, AIs should not be used in premenopausal women because they can paradoxically increase estrogen secretion and may therefore stimulate tumor progression. In perimenopausal women undergoing treatment for breast cancer, it can be difficult to determine true menopausal status because adjuvant chemotherapy, tamoxifen, and gonadotropin-releasing hormone analogues can induce transient (or permanent) ovarian suppression. How can one determine whether these women are truly postmenopausal and therefore candidates for AI therapy? A panel of experts in the field of endocrine therapy in breast cancer met in Dubrovnik, Croatia, on October 23, 2006, to discuss this clinical dilemma. This report summarizes the conclusions and recommendations that arose from this discussion. [Copyright &y& Elsevier]

Abstract: The incidence of second non-breast primary cancer following adjuvant treatment was evaluated using data from patients enrolled from 1978 to 1999 in four International Breast Cancer Study Group (IBCSG) trials. The occurrence of these tumours as sites of the first failure was assessed separately for two treatment comparisons: toremifene versus tamoxifen for 5 years in 1035 patients in IBCSG Trials 12-93 and 14-93 with a median follow-up of 8 years and endocrine therapy (toremifene or tamoxifen) versus chemo-endocrine therapy (CMF or AC plus toremifene or tamoxifen) in 1731 patients from IBCSG Trials III, VII and 12-93, with a combined median follow-up of 14 years. No significant differences in second non-breast primary tumours were observed in either comparison. In particular, the incidences of second primary uterine tumours with toremifene and tamoxifen were similar and no significant increase of secondary leukaemias was observed with chemo-endocrine therapy compared with endocrine therapy. [Copyright &y& Elsevier]