Hypothyroidism may occur as a late effect of breast cancer-directed treatment, particularly after radiotherapy, but little is known whether hypothyroidism affects the prognosis after breast cancer. We investigated the association between hypothyroidism and breast cancer recurrence, and all-cause mortality. In this population-based cohort study, we used national medical registries to identify all Danish women 35 years or older diagnosed with stage I–III, operable breast cancer between 1996 and 2009. Hypothyroidism was defined as hospital diagnoses ascertained via diagnostic codes, or as prescriptions for levothyroxine. Two analytic models were used: (i) hypothyroidism present at the time of the breast cancer diagnosis (prevalent) and (ii) hypothyroidism diagnosed during follow-up as a time-varying exposure lagged by 1 year (incident). Breast cancer recurrence was defined as any local, regional, or distant recurrence or contralateral breast cancer. All-cause mortality included death from any cause in any setting. We used Cox regression models accounting for competing risks to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer recurrence and all-cause mortality. The study cohort included 35,463 women with breast cancer with 212,641 person-years of follow-up. At diagnosis, 1272 women had hypothyroidism and 859 women developed hypothyroidism during follow-up. In total, 5810 patients developed recurrent breast cancer. Neither prevalent nor incident hypothyroidism was associated with breast cancer recurrence (adjusted HRprevalent 1.01, 95% CI 0.87–1.19; adjusted HRincident 0.93, 95% CI 0.75–1.16, respectively). Furthermore, no differences were seen for all-cause mortality for prevalent or incident hypothyroidism (adjusted HRprevalent 1.02, 95% CI 0.92–1.14, and HRincident 1.08, 95% CI 0.95–1.23, respectively). Stratification by menopausal status, oestrogen receptor status, chemotherapy, or radiotherapy did not alter the estimates. Hypothyroidism present at diagnosis or during follow-up was not associated with breast cancer recurrence or all-cause mortality in women with breast cancer. Our findings provide reassurance to patients and their physicians that hypothyroidism is unlikely to impact on the clinical course of breast cancer or survival.

Temperature has profound effects on biochemical processes as suggested by the extensive variation in performance of organisms across temperatures. Nonetheless, the use of fluctuating temperature (FT) regimes in laboratory experiments compared to constant temperature (CT) regimes is still mainly applied in studies of model organisms. We investigated how two amplitudes of developmental temperature fluctuation (22.5/27.5 °C and 20/30 °C, 12/12 h) affected several fitness-related traits in five Drosophila species with markedly different thermal resistance. Egg-to-adult viability did not change much with temperature except in the cold-adapted D. immigrans. Developmental time increased with FT among all species compared to the same mean CT. The impact of FT on wing size was quite diverse among species. Whereas wing size decreased quasi-linearly with CT in all species, there were large qualitative differences with FT. Changes in wing aspect ratio due to FT were large compared to the other traits and presumably a consequence of thermal stress. These results demonstrate that species of the same genus but with different thermal resistance can show substantial differences in responses to fluctuating developmental temperatures not predictable by constant developmental temperatures. Testing multiple traits facilitated the interpretation of responses to FT in a broader context.

Elevated temperatures are expected to rise beyond what the physiology of many organisms can tolerate. Behavioural responses facilitating microhabitat shifts may mitigate some of this increased thermal selection on physiology, but behaviours are themselves mediated by physiology, and any behavioural response may trade-off against other fitness-related activities. We investigated whether experimental evolution in different thermal regimes (Cold: 15 °C; Hot: 31 °C; Intergenerational fluctuation 15/31 °C; Control: 23 °C) resulted in genetic differentiation of standard locomotor activity in the dung fly Sepsis punctum. We assessed individual locomotor performance, an integral part of most behavioral repertoires, across eight warm temperatures from 24 °C to 45 °C using an automated device. We found no evidence for generalist-specialist trade-offs (i.e. changes in the breadth of the performance curve) for this trait. Instead, at the warmest assay temperatures hot-selected flies showed somewhat higher maximal performance than all other, especially cold-selected flies, overall more so in males than females. Yet, the flies' temperature optimum was not higher than that of the cold-selected flies, as expected under the 'hotter-is-better' hypothesis. Maximal locomotor performance merely weakly increased with body size. These results suggest that thermal performance curves are unlikely to evolve as an entity according to theory, and that locomotor activity is a trait of limited use in revealing thermal adaptation.

Purpose: Premenopausal women diagnosed with estrogen receptor (ER) positive breast cancer are prescribed 5–10 years of endocrine therapy to prevent or delay recurrence. Many women who initiate endocrine therapy fail to complete the recommended course of treatment. In this study, we evaluated the association between early discontinuation of adjuvant endocrine therapy and breast cancer recurrence in a cohort of premenopausal women. Patients and Methods: We identified 4,503 premenopausal ER+ breast cancer patients who initiated adjuvant endocrine therapy and were registered in the Danish Breast Cancer Group clinical database (2002–2011). Women were excluded if they had a recurrence or were lost to follow-up less than 1.5 years after breast cancer surgery. Endocrine therapy was considered complete if the patient received at least 4.5 years of treatment or discontinued medication less than 6 months before recurrence. Exposure status was updated annually and modeled as a time-dependent variable. We accounted for baseline and time-varying confounders via time-varying weights, which we calculated from multivariable logistic regression models and included in regression models to estimate hazard ratios (HR) and accompanying 95% confidence intervals (CI) associating early discontinuation with breast cancer recurrence. Results: Over the course of follow-up, 1,001 (22%) women discontinued endocrine therapy. We observed 202 (20%) recurrences among those who discontinued endocrine therapy, and 388 (11%) among those who completed the recommended treatment. The multivariable-adjusted estimated rate of recurrence was higher in women who discontinued endocrine therapy relative to those who completed their treatment (HR=1.67, 95% CI 1.25, 2.14). Conclusion: These results highlight the importance of clinical follow-up and behavioral interventions that support persistence of adjuvant endocrine therapy to prevent breast cancer recurrence.