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.
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.
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.
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.
Earlier diagnosis and more effective treatments mean that the estimated number of cancer survivors in the United Kingdom is expected to reach 4 million by 2030. However, there is an increasing ...realisation that excess body fatness (EBF) is likely to influence the quality of cancer survivorship and disease-free survival. For decades, the discussion of weight management in patients with cancer has been dominated by concerns about unintentional weight loss, low body weight and interventions to increase weight, often re-enforced by the existence of the obesity paradox, which indicates that high body weight is associated with survival benefits for some types of cancer. However, observational evidence provides strong grounds for testing the hypothesis that interventions for promoting intentional loss of body fat and maintaining skeletal muscle in overweight and obese cancer survivors would bring important health benefits in terms of survival outcomes and long-term impact on treatment-related side effects. In this paper, we outline the need for studies to improve our understanding of the health benefits of weight-loss interventions, such as hypocaloric healthy-eating plans combined with physical activity. In particular, complex intervention trials that are pragmatically designed are urgently needed to develop effective, clinically practical, evidence-based strategies for reducing EBF and optimising body composition in people living with and beyond common cancers.
Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer the ...presence of CLS has been correlated to high body mass index (BMI), larger mammary adipocyte size and postmenopausal status. However, the prognostic significance of CLS in HER2 + breast cancer is still unknown. We investigated the prognostic significance of CLS in a cohort of 69 trastuzumab-naïve and 117 adjuvant trastuzumab-treated patients with primary HER2 + breast cancer. Immunohistochemistry of tumour blocks was performed for CLS and correlated to clinical outcomes. CLS were more commonly found at the adipose-tumour border (B-CLS) (64.8% of patients). The presence of multiple B-CLS was associated with reduced time to metastatic disease (TMD) in trastuzumab treated patients with BMI ≥ 25 kg/m
but not those with BMI < 25 kg/m
. Phenotypic analysis showed the presence of CD32B + B-CLS was strongly correlated to BMI ≥ 25 kg/m
and reduced TMD in trastuzumab treated patients. Multivariable analysis suggested that CD32B + B-CLS positive tumours are associated with shorter TMD in trastuzumab-treated patients (HR 4.2 95%CI, (1.01-17.4). This study indicates adipose-tumour border crown-like structures that are CD32B + potentially represent a biomarker for improved personalisation of treatment in HER2-overexpressed breast cancer patients.
ObjectivesPotentially modifiable risk factors account for approximately 23% of breast cancers, with obesity and alcohol being the two greatest. Breast screening and symptomatic clinical attendances ...provide opportunities (‘teachable moments’) to link health promotion and breast cancer-prevention advice within established clinical pathways. This study explored knowledge and attitudes towards alcohol as a risk factor for breast cancer, and potential challenges inherent in incorporating advice about alcohol health risks into breast clinics and screening appointments.DesignA mixed-method study including a survey on risk factors for breast cancer and understanding of alcohol content. Survey results were explored in a series of five focus groups with women and eight semi-structured interviews with health professionals.SettingWomen attending NHS Breast Screening Programme (NHSBSP) mammograms, symptomatic breast clinics and healthcare professionals in those settings.Participants205 women were recruited (102 NHSBSP attenders and 103 symptomatic breast clinic attenders) and 33 NHS Staff.ResultsAlcohol was identified as a breast cancer risk factor by 40/205 (19.5%) of attenders and 16/33 (48.5%) of staff. Overall 66.5% of attenders drank alcohol, and 56.6% could not estimate correctly the alcohol content of any of four commonly consumed alcoholic drinks. All women agreed that including a prevention-focussed intervention would not reduce the likelihood of their attendance at screening mammograms or breast clinics. Qualitative data highlighted concerns in both women and staff of how to talk about alcohol and risk factors for breast cancer in a non-stigmatising way, as well as ambivalence from specialist staff as to their role in health promotion.ConclusionsLevels of alcohol health literacy and numeracy were low. Adding prevention interventions to screening and/or symptomatic clinics appears acceptable to attendees, highlighting the potential for using these opportunities as ‘teachable moments’. However, there are substantial cultural and systemic challenges to overcome if this is to be implemented successfully.
It is not clear how the pathology, presentation and outcome for patients who present with de novo metastatic breast cancer (dnMBC) compare with those who later develop distant metastases. DnMBC is ...uncommon in younger patients. We describe these differences within a cohort of young patients in the United Kingdom.
Women aged 40 years or younger with a first invasive breast cancer were recruited to the prospective POSH national cohort study. Baseline clinicopathological data were collected, with annual follow-up. Overall survival (OS) and post-distant relapse-free survival (PDRS) were assessed using Kaplan-Meier curves.
In total, 862 patients were diagnosed with metastatic disease. DnMBC prevalence was 2.6% (76/2977). Of those with initially localised disease, 27.1% (786/2901) subsequently developed a distant recurrence. Median follow-up was 11.00 years (95% CI 10.79-11.59). Patients who developed metastatic disease within 12 months had worse OS than dnMBC patients (HR 2.64; 1.84-3.77). For PDRS, dnMBC was better than all groups, including those who relapsed after 5 years. Of dnMBC patients, 1.3% had a gBRCA1, and 11.8% a gBRCA2 mutation.
Young women with dnMBC have better PDRS than those who develop relapsed metastatic breast cancer. A gBRCA2 mutation was overrepresented in dnMBC.
It is clear both from our data and that of Kelly Metcalfe and colleagues that long-term survivors of breast cancer with BRCA mutations will probably benefit from bilateral mastectomy.1,2 However, ...patients will only benefit from avoiding a future primary breast cancer if they survive their first diagnosis.
The impact of living with metastatic breast cancer (MBC) is considerable and psychosocial support can be beneficial. Mindfulness-based stress reduction (MBSR) can help self-management of anxiety, ...depression, quality of life (QoL), and fatigue and has been evaluated in early-stage breast cancer but not MBC. This study investigated the acceptability and feasibility of providing MBSR for women with MBC and of introducing MBSR into a National Health Service (NHS) setting. A mixed methods convergent design was used. Eligible women with MBC, an Eastern Cooperative Oncology Group (ECOG) score of 0 to 2, stable disease, and life expectancy of at least 6 months were invited to attend (by their oncologist) an 8-week MBSR course. Qualitative interviews with patients, a focus group, and interview with NHS staff were held to explore acceptability and feasibility of MBSR. Questionnaires at baseline, during (weeks 4, 8), and after (weeks 16, 24) the course measured fatigue, anxiety and depression, mindfulness, disease-specific QoL, and generic preference based QoL. Of 100 women approached, 20 joined the study. One woman dropped out prior to the intervention due to illness progression. Nineteen women took part in 3 MBSR courses. Recruitment to 2 of the 3 courses was slow. Commitment to 8 weeks was a reason for non-participation, and proved challenging to participants during the course. Participants found the course acceptable and reported many cumulative and ongoing benefits. These included feeling less reactive to emotional distress and more accepting of the disruption to life that occurs with living with MBC. There was high attendance, completion of course sessions, adherence to home practice, excellent follow-up rates, and high questionnaire return rates. MBSR was acceptable to MBC patients, who perceived benefits such as improved anxiety and QoL; but the MBSR course requires a considerable time commitment. There is scope to tailor the intervention so that it is less intensive.
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