Retrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine ...the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer.
We did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing.
Between Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0–9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% 95% CI 94·5–98·4 vs 96·6% 95·8–97·3; at 5 years: 83·8% 79·3–87·5 vs 85·0% 83·5–86·4; at 10 years: 73·4% 67·4–78·5 vs 70·1% 67·7–72·3; hazard ratio HR 0·96 95% CI 0·76–1·22; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% 95% CI 89–97 vs 91% 88–94; HR 0·59 95% CI 0·35–0·99; p=0·047) but not 5 years (81% 73–87 vs 74% 70–78; HR 1·13 0·70–1·84; p=0·62) or 10 years (72% 62–80 vs 69% 63–74; HR 2·12 0·82–5·49; p= 0·12).
Patients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences.
Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.
Breast cancer is the most commonly diagnosed cancer worldwide and is one of the leading causes of cancer death. The incidence, pathological features, and clinical outcomes in breast cancer differ by ...geographical distribution and across racial and ethnic populations. Importantly, racial and ethnic diversity in breast cancer clinical trials is lacking, with both Blacks and Hispanics underrepresented. In this forum article, breast cancer researchers from across the globe discuss the factors contributing to racial and ethnic breast cancer disparities and highlight specific implications of precision oncology approaches for equitable provision of breast cancer care to improve outcomes and address disparities.
Breast cancer is the most common cancer diagnosis in women aged less than 40 years and the second most common cause of cancer death in this age group. Global rates of young onset breast cancer have ...risen steadily over the last twenty years. Although young women with breast cancer have a higher frequency of underlying pathogenic mutations in high penetrance breast cancer susceptibility genes (CSG) than older women, the vast majority of young breast cancer patients are not found to have a germline CSG mutation. There is therefore a need to inform young women regarding non-genetic breast cancer risk factors which have the potential to be influenced by changes in individual behaviour. A Pubmed search was performed using the search terms "young" or "early onset", and "breast cancer" and "modifiable risk". Titles and abstracts from peer-reviewed publications were screened for relevance. This review presents evidence for potentially modifiable risk factors of breast cancer risk in young women, including lifestyle factors (physical activity, body habitus, alcohol use, smoking, shift work and socioeconomic factors), reproductive and hormonal factors and iatrogenic risks. The extent to which these factors are truly modifiable is discussed and interactions between genetic and non-genetic risk factors are also addressed. Health care professionals have an opportunity to inform young women about breast health and risk when presenting at a "teachable moment", including the benefits of physical activity and alcohol habits as risk factor. More focussed discussions regarding individual personal risk and benefit should accompany conversations regarding reproductive health and take into consideration both non-modifiable and iatrogenic BC risk factors.
The incidences of both breast cancer and obesity are rising in the UK. Obesity increases the risk of developing breast cancer in the postmenopausal population and leads to worse outcomes in those of ...all ages treated for early-stage breast cancer. In this review we explore the multifactorial reasons behind this association and the clinical trial evidence for the benefits of physical activity and dietary interventions in the early and metastatic patient groups. As more people with breast cancer are cured, and those with metastatic disease are living longer, cancer survivorship is becoming increasingly important. Therefore, ensuring the long-term implications of cancer and cancer treatment are addressed is vital. Although there remains a lack of definitive evidence that deliberate weight loss after a diagnosis of breast cancer reduces disease recurrence, a number of studies have reported benefits of weight loss and of physical activity. However, the limited data currently available mean that clinicians remain unclear on the optimal lifestyle advice to give their patients. Further high-quality research is needed to provide this evidence base, which will be required to optimise clinical care and for the commissioning of lifestyle interventions in the UK in breast cancer survivors.
Mastectomy skin flap necrosis (MSFN) has a reported incidence of 5%-30% in the literature. It is often a significant and underappreciated problem. The aim of this article was to review the associated ...challenges and possible solutions.
A MEDLINE search was performed using the search term "mastectomy skin flap necrosis". Titles and abstracts from peer-reviewed publications were screened for relevance.
MSFN is a common complication and may present as partial- or full-thickness necrosis. Predictive patient risk factors include smoking, diabetes, obesity, radiotherapy, previous scars and severe medical comorbidity. MSFN leads to a number of challenges, including wound management problems, delays to adjuvant therapy, esthetic compromise, implant extrusion, patient distress and financial loss. Careful preoperative planning and meticulous surgical technique may reduce the incidence of MSFN. A number of intraoperative techniques are available to try and predict skin flaps at risk of MSFN. MSFN may be managed operatively or nonoperatively. Early intervention may reduce the morbidity of MSFN in selected cases. Topical nitroglycerin ointment may be beneficial in reducing MSFN following immediate reconstruction, but the evidence base is still limited.
MSFN can result in considerable challenges for the patient and the health care service. This review discusses the management options for this problem.
Purpose
A James Lind Alliance priority setting partnership was developed to identify research priorities in breast cancer surgery from individuals with lived experience, at high genetic risk of ...breast cancer, and healthcare professionals (HCPs).
Methods
‘Uncertainties’ were collected using an online survey. Following an evidence check and development of summary questions, an interim survey asked participants to rank their top 10 research priorities from the question list. Top-ranked questions from patient/carer, high-risk and professional groups were carried forward for discussion to a final online prioritisation workshop.
Results
260 participants (101 patients/carers, 156 HCPs) submitted 940 uncertainties via the initial survey. These were analysed thematically into 128 summary questions in six topic areas. Following evidence checking, 59 questions were included in the interim survey which was completed by 572 respondents. Marked differences were seen in questions prioritised by patients/carers, HCPs and women at high-risk. The top eight priorities in patient/carer and professional groups and top two priorities for high-risk women were carried forward to the online workshop at which 22 participants discussed and agreed the final top 10. Key themes included de-escalation of breast and axillary surgery, factors impacting the development/detection of locoregional recurrence and optimal provision of support for informed treatment decision-making.
Conclusion
The top 10 research priorities in breast cancer surgery have been agreed. However, the observed differences in research priorities identified by patients and professional groups were not anticipated. Top priorities from both groups should inform future UK breast cancer surgical research, to ensure that it addresses questions that are important to breast cancer community as a whole.
Cancer is a leading cause of disease burden globally, with more than 19·3 million cases and 10 million deaths recorded in 2020. Research is crucial to understanding the determinants of cancer and the ...effects of interventions, and to improving outcomes. We aimed to analyse global patterns of public and philanthropic investment in cancer research.
In this content analysis, we searched the UberResearch Dimensions database and Cancer Research UK data for human cancer research funding awards from public and philanthropic funders between Jan 1, 2016, and Dec 31, 2020. Included award types were project and programme grants, fellowships, pump priming, and pilot projects. Awards focused on operational delivery of cancer care were excluded. Awards were categorised by cancer type, cross-cutting research theme, and research phase. Funding amount was compared with global burden of specific cancers, measured by disability-adjusted life-years, years lived with disability, and mortality using data from the Global Burden of Disease study.
We identified 66 388 awards with total investment of about US$24·5 billion in 2016–20. Investment decreased year-on-year, with the largest drop observed between 2019 and 2020. Pre-clinical research received 73·5% of the funding across the 5 years ($18 billion), phase 1–4 clinical trials received 7·4% ($1·8 billion), public health research received 9·4% ($2·3 billion), and cross-disciplinary research received 5·0% ($1·2 billion). General cancer research received the largest investment ($7·1 billion, 29·2% of the total funding). The most highly funded cancer types were breast cancer ($2·7 billion 11·2%), haematological cancer ($2·3 billion 9·4%), and brain cancer ($1·3 billion 5·5%). Analysis by cross-cutting theme revealed that 41·2% of investment ($9·6 billion) went to cancer biology research, 19·6% ($4·6 billion) to drug treatment research, and 12·1% ($2·8 billion) to immuno-oncology. 1·4% of the total funding ($0·3 billion) was spent on surgery research, 2·8% ($0·7 billion) was spent on radiotherapy research, and 0·5% ($0·1 billion) was spent on global health studies.
Cancer research funding must be aligned with the global burden of cancer with more equitable funding for cancer research in low-income and middle-income countries (which account for 80% of cancer burden), both to support research relevant to these settings, and build research capacity within these countries. There is an urgent need to prioritise investment in surgery and radiotherapy research given their primacy in the treatment of many solid tumours.
None.
To assess clinical and surgical factors affecting local recurrence and survival in young breast cancer patients in the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer ...(POSH).
Emerging data suggest young age is a predictor of increased local recurrence.
POSH is a prospective cohort of 3024 women of 18 to 40 years with breast cancer. Cohort characteristics were grouped by mastectomy or BCS. Endpoints were local-recurrence interval (LRI), distant disease-free interval (DDFI), and overall survival (OS); described using cumulative-hazard and Kaplan-Meier plots and multivariable analyses by Flexible Parametric and Cox regression models.
Mastectomy was performed in 1464 patients and breast-conserving surgery (BCS) in 1395. Patients undergoing mastectomy had larger tumors and higher proportions of positive family history, estrogen receptor+, progesterone receptor+, and/or human epidermal growth factor receptor 2+ tumors. Local events accounted for 15% of recurrences. LRI by surgical type varied over time with LRI similar at 18 months (1.0% vs 1.0%, P = 0.348) but higher for BCS at 5 and 10 years (5.3% vs 2.6%, P < 0.001; and 11.7% vs 4.9%, P < 0.001, respectively). Similar results were found in the adjusted model. Conversely, distant-metastases and deaths were lower for BCS but not after adjusting for prognostic factors. After mastectomy chest-wall radiotherapy was associated with improved LRI (hazard ratio, HR = 0.46, P = 0.015). Positive surgical margins, and development of local recurrence predicted for reduced DDFI (HR = 0.50, P < 0.001; and HR = 0.29, P = 0.001, respectively).
Surgical extent appears less important for DDFI than completeness of excision or, where appropriate, chest-wall radiotherapy. Despite higher local-recurrence rates for BCS, surgical type does not influence DDFI or OS after adjusting for known prognostic factors in young breast cancer patients.
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