Explore the vast range of titles available.

Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964–86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76–1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89–1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57–0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67–0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fluorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55–0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64–0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69–0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77–0·99, 2p=0·04). After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy. Cancer Research UK, British Heart Foundation, UK Medical Research Council.

Screening Mammography and Breast-Cancer Incidence Mammography detects substantially more cases of early-stage breast cancer, but late-stage diagnoses have decreased little. This study shows that up to 31% of new breast cancers may be overdiagnosed, although it is not known which tumors may have a fatal course. There are two prerequisites for screening to reduce the rate of death from cancer. 1 , 2 First, screening must advance the time of diagnosis of cancers that are destined to cause death. Second, early treatment of these cancers must confer some advantage over treatment at clinical presentation. Screening programs that meet the first prerequisite will have a predictable effect on the stage-specific incidence of cancer. As the time of diagnosis is advanced, more cancers will be detected at an early stage and the incidence of early-stage cancer will increase. If the time of diagnosis of cancers that will progress to a . . .

A large study shows that irradiation of the chest in women with breast cancer delivers an average of about 5 Gy and that the risk of a subsequent coronary event increases at a rate of 7.4% per gray in a linear fashion, without a threshold and with no apparent decline over time. Randomized trials have shown that radiotherapy for early-stage breast cancer can reduce the rates of recurrence and of death from breast cancer. 1 , 2 However, long-term follow-up in some trials has shown that radiotherapy can also increase the risk of ischemic heart disease, presumably through incidental irradiation of the heart. 1 , 3 Radiotherapy regimens for breast cancer have changed since the women in these trials were irradiated, and the doses of radiation to which the heart is exposed are now generally lower. 4 Nevertheless, in most women, the heart still receives doses of 1 to 5 Gy. 5 – 11 Several studies have suggested that . . .

Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer. This review focuses on its origin, molecular and clinical characteristics, and treatment. A PubMed search of the medical literature shows that the first mention of “triple-negative” breast cancer was in October 2005; since then, the term has appeared in more than 600 publications. 1 This increase reflects the growing recognition of the importance of triple-negative breast cancer (see the Glossary for this and other key terms) by oncologists, pathologists, and geneticists, as well as by the approximately 12 to 17% of women with breast cancer who have triple-negative breast cancer. As a group, patients with triple-negative tumors have a relatively poor outcome and cannot be treated with endocrine therapy or therapies targeted to . . .

The breast cancer screening programmes in the United Kingdom currently invite women aged 50-70 years for screening mammography every 3 years. Since the time the screening programmes were established, there has been debate, at times sharply polarised, over the magnitude of their benefit and harm, and the balance between them. The expected major benefit is reduction in mortality from breast cancer. The major harm is overdiagnosis and its consequences; overdiagnosis refers to the detection of cancers on screening, which would not have become clinically apparent in the woman's lifetime in the absence of screening. Professor Sir Mike Richards, National Cancer Director, England, and Dr Harpal Kumar, Chief Executive Officer of Cancer Research UK, asked Professor Sir Michael Marmot to convene and chair an independent panel to review the evidence on benefits and harms of breast screening in the context of the UK breast screening programmes. The panel, authors of this report, reviewed the extensive literature and heard testimony from experts in the field who were the main contributors to the debate. 85 references

A multinational study of 154 families with PALB2 mutations shows that mutation carriers have a 14% risk of breast cancer by 50 years of age and a 35% risk by 70 years of age, which is similar to the risk associated with BRCA2 mutations. PALB2 (partner and localizer of BRCA2) was originally identified as a BRCA2-interacting protein that is crucial for key BRCA2 genome caretaker functions 1 , 2 ; it was subsequently also shown to interact with BRCA1. 3 Biallelic germline loss-of-function mutations in PALB2 (also known as FANCN ) cause Fanconi’s anemia, whereas monoallelic loss-of-function mutations are associated with an increased risk of breast cancer and pancreatic cancer. 4 Previous studies of familial breast cancer have yielded estimates of risk in association with loss-of-function mutations in PALB2 that are two to four times as high as the risk among non–mutation carriers. 5 – 7 In Finland, the PALB2 . . .

This study evaluated the sensitivity of assaying tumor DNA circulating in the plasma to monitor breast cancer. This assay is compared with three other approaches: radiographic imaging, assay of cancer antigen 15-3 (CA 15-3) levels, and assay of circulating tumor cells. Breast cancer is the most common cancer and the leading cause of cancer-related death in women worldwide. 1 Metastatic breast cancer remains an incurable disease but is treatable by means of serial administration of endocrine, cytotoxic, or biologic therapies. The monitoring of treatment response is essential to avoid continuing ineffective therapies, to prevent unnecessary side effects, and to determine the benefit of new therapeutics. Treatment response is generally assessed with the use of serial imaging, but radiographic measurements often fail to detect changes in tumor burden. Therefore, there is an urgent need for biomarkers that measure tumor burden with high sensitivity . . .

Objectives: Perturbations in mammary gland (MG) development may increase risk for later adverse effects, including lactation impairment, gynecomastia (in males), and breast cancer. Animal studies indicate that exposure to hormonally active agents leads to this type of developmental effect and related later life susceptibilities. In this review we describe current science, public health issues, and research recommendations for evaluating MG development. Data Sources: The Mammary Gland Evaluation and Risk Assessment Workshop was convened in Oakland, California, USA, 16-17 November 2009, to integrate the expertise and perspectives of scientists, risk assessors, and public health advocates. Interviews were conducted with 18 experts, and seven laboratories conducted an MG slide evaluation exercise. Workshop participants discussed effects of gestational and early life exposures to hormonally active agents on MG development, the relationship of these developmental effects to lactation and cancer, the relative sensitivity of MG and other developmental end points, the relevance of animal models to humans, and methods for evaluating MG effects. Synthesis: Normal MG development and MG carcinogenesis demonstrate temporal, morphological, and mechanistic similarities among test animal species and humans. Diverse chemicals, including many not considered primarily estrogenic, alter MG development in rodents. Inconsistent reporting methods hinder comparison across studies, and relationships between altered development and effects on lactation or carcinogenesis are still being defined. In some studies, altered MG development is the most sensitive endocrine end point. Conclusions: Early life environmental exposures can alter MG development, disrupt lactation, and increase susceptibility to breast cancer. Assessment of MG development should be incorporated in chemical test guidelines and risk assessment.

Whether breast cancer screening does more harm than good has been debated extensively. The main questions are how large the benefit of screening is in terms of reduced breast cancer mortality and how substantial the harm is in terms of overdiagnosis, which is defined as cancers detected at screening that would not have otherwise become clinically apparent in the woman's lifetime. An independent Panel was convened to reach conclusions about the benefits and harms of breast screening on the basis of a review of published work and oral and written evidence presented by experts in the subject. To provide estimates of the level of benefits and harms, the Panel relied mainly on findings from randomised trials of breast cancer screening that compared women invited to screening with controls not invited, but also reviewed evidence from observational studies. The Panel focused on the UK setting, where women aged 50–70 years are invited to screening every 3 years. In this Review, we provide a summary of the full report on the Panel's findings and conclusions. In a meta-analysis of 11 randomised trials, the relative risk of breast cancer mortality for women invited to screening compared with controls was 0·80 (95% CI 0·73–0·89), which is a relative risk reduction of 20%. The Panel considered the internal biases in the trials and whether these trials, which were done a long time ago, were still relevant; they concluded that 20% was still a reasonable estimate of the relative risk reduction. The more reliable and recent observational studies generally produced larger estimates of benefit, but these studies might be biased. The best estimates of overdiagnosis are from three trials in which women in the control group were not invited to be screened at the end of the active trial period. In a meta-analysis, estimates of the excess incidence were 11% (95% CI 9–12) when expressed as a proportion of cancers diagnosed in the invited group in the long term, and 19% (15–23) when expressed as a proportion of the cancers diagnosed during the active screening period. Results from observational studies support the occurrence of overdiagnosis, but estimates of its magnitude are unreliable. The Panel concludes that screening reduces breast cancer mortality but that some overdiagnosis occurs. Since the estimates provided are from studies with many limitations and whose relevance to present-day screening programmes can be questioned, they have substantial uncertainty and should be regarded only as an approximate guide. If these figures are used directly, for every 10 000 UK women aged 50 years invited to screening for the next 20 years, 43 deaths from breast cancer would be prevented and 129 cases of breast cancer, invasive and non-invasive, would be overdiagnosed; that is one breast cancer death prevented for about every three overdiagnosed cases identified and treated. Of the roughly 307 000 women aged 50–52 years who are invited to begin screening every year, just over 1% would have an overdiagnosed cancer in the next 20 years. Evidence from a focus group organised by Cancer Research UK and attended by some members of the Panel showed that many women feel that accepting the offer of breast screening is worthwhile, which agrees with the results of previous similar studies. Information should be made available in a transparent and objective way to women invited to screening so that they can make informed decisions.

For 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. In 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. Among 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 (688 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·78). 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 0·75 (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%). For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.