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Background Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. Methods We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. Results Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. Conclusions Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

Although l -DOPA represents the standard of care in Parkinson's disease, long-term treatment may be compromised by l -DOPA-induced dyskinesia (LID), with adverse fluctuations in motor responsiveness and progressive loss of control. Here we show that in rats with 6-hydroxydopamine-induced lesions of the median forebrain bundle, LID correlates with 5-HT levels. Rats were treated with l -DOPA (6 mg/kg) and benserazide (15 mg/kg) daily for 3 weeks to induce the development of abnormal involuntary movements (AIMs). After this chronic l -DOPA treatment, the lesion side of the rats displayed significant changes in striatal dopamine (DA) and 5-HT levels. Striatal DA and 5-hydroxytryptamine (5-HT) levels were inversely correlated, and AIMs were strongly positively correlated with DA levels and negatively correlated with 5-HT levels. Axial AIMs were more strongly correlated with DA and 5-HT levels than were the other AIMs subtypes, while locomotive AIMs showed no significant correlation at all. In addition, striatal 5-HT was more strongly (negatively) correlated with the AIMs than striatal DA levels. These results demonstrate that 5-HT contributes to LID and that both striatal DA (positively) and 5-HT (negatively) affect the severity of LID. We suggest that by strategic modification of the serotonin system it may be possible to attenuate the adverse effects of chronic l -DOPA therapy.