SummaryBackgroundFor women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years.MethodsIn the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633.FindingsAmong women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%).InterpretationFor women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurren...

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Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case-control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5'-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms.

Background: Cediranib (RECENTIN™) is a highly potent VEGF signaling inhibitor that has shown clinical activity across a range of tumors at doses of 20, 30 and 45 mg, both as monotherapy and in combination with other agents. Fulvestrant (FASLODEX™) is a selective estrogen-receptor antagonist with no agonist effects that is effective in patients (pts) with hormone-sensitive, postmenopausal metastatic breast cancer (MBC) who have progressed or recurred on prior hormonal therapy. This randomized screening study evaluated cediranib in combination with fulvestrant.Methods: Eligible pts were postmenopausal women with histologically/cytologically confirmed hormone-sensitive MBC with measurable or non-measurable disease, no prior anti-VEGF or fulvestrant treatment and ≤1 prior cytotoxic chemotherapy. Pts received once-daily oral cediranib 45 mg or placebo, both in combination with fulvestrant (loading dose schedule: 500 mg im [2 x 250 mg] on day 1, 250 mg im on day 14, then 250 mg im every month). The primary objective was to determine whether cediranib + fulvestrant prolonged progression-free survival (PFS) vs placebo + fulvestrant (≥80% power to detect a hazard ratio [HR] of 0.50; P<0.2). Secondary assessments included objective response rate (complete response [CR] + partial response [PR]; only pts with measurable disease at baseline), duration of response (DoR), clinical benefit rate (CR + PR + stable disease ≥6 months), determination of any pharmacokinetic interaction, safety and tolerability.Results: Sixty-two pts were randomized to cediranib + fulvestrant (n=31) or placebo + fulvestrant (n=31). Baseline characteristics were balanced between arms with a median of 2 prior hormonal therapies in each arm. PFS in pts treated with cediranib + fulvestrant showed a numerical advantage vs placebo + fulvestrant that was not statistically significant (HR 0.867; 95% CI 0.450–1.669; P=0.669). The objective response rate was 22% (n=4 PRs; median DoR=208 days) for cediranib + fulvestrant vs 8% (n=1 PR; DoR =224 days) for placebo + fulvestrant. The clinical benefit rate was 42% (n=13) in both arms. There was no evidence of a clinically relevant effect of cediranib on the pharmacokinetics of fulvestrant. The most common adverse events (AEs) in pts receiving cediranib + fulvestrant were diarrhea (68%), fatigue (61%) and hypertension (55%). The cediranib + fulvestrant arm showed a higher incidence of CTCAE grade ≥3 AEs (68% vs 32%), serious AEs (48% vs 13%), AEs leading to discontinuation of cediranib/placebo (39% vs 10%), and cediranib/placebo dose reductions or pauses (74% vs 32%). No new unexpected toxicities or clinical laboratory findings were observed with cediranib + fulvestrant and the AE profile was consistent with previous studies of cediranib 45 mg. There were two deaths in the placebo + fulvestrant arm during the study: sepsis from a leg ulcer, and respiratory failure in a pt with pulmonary metastases, emphysema and pleural effusion.Conclusions: Cediranib 45 mg + fulvestrant 250 mg demonstrated clinical activity in MBC but cediranib did not appear to be sufficiently well tolerated at this dose. Future studies of cediranib in this setting should be considered using lower doses in combination with hormonal agents/chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 204.

Erythropoietic protoporphyria (EPP) is an autosomal recessive deficiency in heme biosynthesis due to pathogenic variants in the ferrochelatase gene ( FECH ). Patients present with lifelong photosensitivity and potential liver disease. Here we report a novel FECH variant designated c.904_912+1del found in trans with the c.315-48T>C hypomorphic variant, in one family with three affected individuals. These patients presented with immediate painful cutaneous photosensitivity but no hepatic manifestations. All have elevated protoporphyrin levels consistent with a diagnosis of EPP. Genetic, biochemical, and functional assay results obtained for this family suggest that the unique variant c.904_912+1del is likely pathogenic and thus causative of EPP.

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Objetivo: identificar o conhecimento dos graduandos de enfermagem acerca dos protocolos de atendimento à mulher vítima de violência. Método: pesquisa do tipo exploratório, descritivo, de abordagem qualitativa, realizado entre junho e agosto de 2022, numa universidade pública, com graduandos de enfermagem matriculados entre o oitavo e décimo semestres. Os dados foram interpretados pela análise de conteúdo temática. Resultados: três categorias foram construídas: Conhecimento dos graduandos acerca da violência contra mulher e dos protocolos de assistência; Reconhecendo a preparação do graduando de enfermagem para a utilização dos protocolos de assistência às vítimas de violência; e Aprendizado acerca da assistência às vítimas de violência. Os graduandos demonstraram o reconhecimento da importância do tema e da atuação do enfermeiro na assistência às mulheres vítimas de violência. Mas apontam a insuficiência na formação. Conclusão: apesar dos entrevistados terem conhecimento sobre a definição de violência doméstica e compreenderem a importância da temática durante a graduação, observou-se lacunas referente ao conhecimento acerca das condutas e protocolos utilizados durante assistência.