Fig. 3: Reduced chemosensitivity during dioestrus in hormone receptor-positive and hormone receptor-negative tumour models.
From: The oestrous cycle stage affects mammary tumour sensitivity to chemotherapy
a,c,e,f, Immunohistochemical staining for ER (left) and PR (right), representative of more than five treatment-naive tumours in more than five mice of the genetic MMTV-Wnt1 (a), transplanted Brca1−/−;Trp53−/− (c) and genetic (e) and transplanted MMTV-PyMT (f) models at oestrus (top) and dioestrus (bottom). b,d, Left, treatment effect in transplanted MMTV-Wnt1 (b) and Brca1−/−;Trp53−/− (d) models, represented as tumour size normalized to initial treatment size. Arrows indicate rounds of treatment, lines the tumour means and shading s.e.m. MMTV-Wnt1 model: n = 5–6 mice per group with O = 6 and D = 6 tumours at first treatment. Brca1−/−;Trp53−/− model: n = 6–8 mice per group, with O = 12 and D = 14 tumours at first treatment. Middle, fitted growth curves of mixed-effects model representing tumour volume for transplanted MMTV-Wnt1 (b) and Brca1−/−;Trp53−/− (d) models. Right, Kaplan–Meier curves for MMTV-Wnt1 (b) and Brca1−/−;Trp53−/− (d) mice treated with doxorubicin initiated during oestrus or dioestrus. MMTV-Wnt1: oestrus, n = 6 mice; dioestrus, n = 5 mice; Brca1−/−;Trp53−/−: oestrus, n = 6 mice; dioestrus n = 8 mice. g, Left, treatment effect in transplanted MMTV-PyMT model, represented as tumour size normalized to initial treatment size. Arrows indicate rounds of treatment, lines the tumour means and shading s.e.m.; n = 8–13 mice per group, with O = 25, D = 15 and OVX = 20 tumours at first treatment. Right, fitted growth curves of mixed-effects model representing tumour volume. b,d,g, Left, significance was determined using nonlinear modelling of tumour growth. Treatment effect is shown until over 40% (b,g) or over 20% (d) of mice reached humane endpoint. Response between groups was statistically evaluated using a joint model (b,d,g, middle); survival analysis was performed using a regression model (b,d,g, right). #P < 0.1, *P < 0.05; **P < 0.01. Scale bars, 150 µm.
