The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated disease (COVID-19) outbreak seriously challenges globally all health care systems and professionals. Expert projections ...estimate that despite social distancing and lockdown being practiced, we have yet to feel the full impact of COVID-19. In this manuscript we provide guidance to prepare for the impact of COVID-19 pandemic on breast cancer patients and advise on how to triage, prioritize and organize diagnostic procedures, surgical, radiation and medical treatments.
Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer (n = 582) enrolled in the Suppression of Ovarian Function Trial (SOFT) ...and Tamoxifen and Exemestane Trial (TEXT). Methods In SOFT, women still premenopausal after surgery with or without chemotherapy were randomly assigned to tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. In TEXT, all received OFS with or without concomitant chemotherapy and were randomly assigned to exemestane plus OFS or tamoxifen plus OFS. We summarize treatment efficacy, quality of life, and adherence of the cohort of women younger than 35 years in SOFT and TEXT, alongside data from the cohort of older premenopausal women. Results For 240 human epidermal growth factor receptor 2-negative patients younger than 35 years enrolled in SOFT after receiving chemotherapy, the 5-year breast cancer-free interval (BCFI) was 67.1% (95% CI, 54.6% to 76.9%) with tamoxifen alone, 75.9% with tamoxifen plus OFS (95% CI, 64.0% to 84.4%), and 83.2% with exemestane plus OFS (95% CI, 72.7% to 90.0%). For 145 human epidermal growth factor receptor 2-negative patients younger than 35 years in TEXT, 5-year BCFI was 79.2% (95% CI, 66.2% to 87.7%) with tamoxifen plus OFS and 81.6% (95% CI, 69.8% to 89.2%) with exemestane plus OFS. The most prominent quality of life symptom for patients younger than 35 years receiving OFS was vasomotor symptoms, with the greatest worsening from baseline at 6 months (on the order of 30 to 40 points), but loss of sexual interest and difficulties in becoming aroused were also clinically meaningful (≥ 8-point change). The level of symptom burden was similar in older premenopausal women. A total of 19.8% of women younger than 35 years stopped all protocol-assigned endocrine therapy early. Conclusion In women younger than 35 years with hormone receptor-positive breast cancer, adjuvant OFS combined with tamoxifen or exemestane produces large improvements in BCFI compared with tamoxifen alone. Menopausal symptoms are significant but are not worse than those seen in older premenopausal women.
Fertility and pregnancy-related issues are major concerns for young breast cancer patients. Limited data are available on physicians' knowledge, attitudes and practice in these fields.
A 26-item ...questionnaire exploring 3 different topics (fertility preservation, pregnancy after breast cancer and breast cancer during pregnancy) was sent by email to physicians attending the 2016 3rd European School of Oncology (ESO) – European Society for Medical Oncology (ESMO) Breast Cancer in Young Women Conference (BCY3) and the 15th St. Gallen International Breast Cancer Conference 2017 (BCC 2017). Given the selected sample, survey respondents were expected to have a higher than average interest in the management of breast cancer patients. Descriptive analyses were performed.
A total of 273 physicians (105 at BCY3 and 168 at BCC 2017) completed the survey; 37.0%, 46.9% and 34.8% reported never having consulted the available international guidelines on fertility preservation, pregnancy after breast cancer and management of breast cancer during pregnancy, respectively.
Up to 18.3% of respondents did not know if the different fertility preservation options were available in their country; 22.3% suggested that controlled ovarian stimulation should not be considered safe in patients with hormone receptor-positive disease. A total of 30.4% of respondents agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence. Regarding breast cancer during pregnancy, 23.8% and 38.1% disagreed or were neutral on the statements that endocrine therapy and anti-HER2 agents should be avoided during pregnancy, respectively.
Further educational initiatives are needed to improve physicians' knowledge and adherence to available guidelines when addressing fertility and pregnancy-related issues in young breast cancer patients.
•Fertility and pregnancy-related issues are major concerns for young breast cancer patients.•Limited data are available on physicians' knowledge, attitudes and practice in these fields.•This survey exploring fertility preservation, pregnancy during and after breast cancer globally showed a positive and encouraging picture.•Nevertheless, adherence to guidelines on these topics in young women with breast cancer remains sub-optimal.•Further educational initiatives are needed to improve physicians' knowledge and adherence to available guidelines.
Despite breast cancer being uncommon in young women, it is still the most frequent cancer diagnosed in women aged 15–39 years, and the leading cause of death in this age group in high-income ...countries, after accidents and self-injury. The present review summarizes the most recent guidelines and offers an expert perspective on the many challenges associated with treatment of young women with breast cancer. We will especially focus on early breast cancer, exploring the specificities of the diagnostic process, imaging techniques, locoregional and systemic treatments, and the added value of dedicated multidisciplinary teams. Specific differences in adjuvant treatment between premenopausal and postmenopausal women, especially regarding endocrine therapy, will be addressed in detail. Research questions and current gaps in important fields, such as the paucity of age-specific data regarding antihuman epidermal growth factor receptor 2 (anti-HER2) therapy and gene panels such as OncotypeDX or MAMMAPRINT will be highlighted. A consistent part of this review is dedicated to the issues defining ‘young women’, such as fertility preservation, managing long-term side effects of oncological treatments and genetic counselling, by detailing current strategies and future perspectives.
Breast Cancer (BC) specialists need to acquire comprehensive knowledge, covering their own specialty and principles of related disciplines. Blended learning, the integration of online and ...face-to-face learning, is becoming more and more important in academic education and has added value during pandemics which limit face-to-face learning and residential training. In this context, the ESO-ULM Certificate of Competence in Breast Cancer (CCB) provides postgraduate multidisciplinary education and delivers an academic postgraduate title. The aim of this work is to investigate the degree of satisfaction of 42 participants to the first two editions of the programme and to assess if attending the programme entailed any professional gain.
An ad-hoc questionnaire was developed exploring 4 areas: participants' characteristics, administrative aspects, CCB Program syllabus and design, professional impact.
The program was attractive for specialists of different disciplines from all over the world: > 90% of responders appreciated the curriculum set up and the quality of the teaching. Despite 64% of responders changed their clinical practice, only 33% could implement institutional changes. One third of the participants activated a collaboration with other colleagues and 64% used the CCB as a trigger to take part in other educational activities. Only 12% of the participants had the opportunity, after CCB, to visit other BC Units or to be involved in international research projects. More than half of the attendees profited from attending CCB in terms of promotions (16.7%), change of working institution (9.5%) or development of a more structured educational program at their home institutions (28.6%).
Results provide interesting and stimulating considerations on the expectations and needs of training physicians and on what modern educational tools and formats can achieve. This paper can provide useful information to navigate through what the post-graduate training market is currently offering to develop a specific curriculum in modern multidisciplinary BC care but might not be applicable to other fields of multidisciplinary oncology.
Summary Background The combined efficacy analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression (OFS) compared with ...tamoxifen plus OFS. We present patient-reported outcomes from these trials. Methods Between Nov 7, 2003, and April 7, 2011, 4717 premenopausal women with hormone-receptor positive breast cancer were enrolled in TEXT or SOFT to receive unmasked adjuvant treatment with 5 years of exemestane plus OFS or tamoxifen plus OFS. Gonadotropin-releasing hormone analogue triptorelin, bilateral oophorectomy, or bilateral ovarian irradiation were used to achieve OFS. Chemotherapy use was optional. Randomisation with permuted blocks was done with the International Breast Cancer Study Group's internet-based system and was stratified by chemotherapy use and status of lymph nodes. Patients completed a quality of life (QoL) form comprising several global and symptom indicators at baseline, every 6 months for 24 months, and then every year during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6 months, 24 months, and 60 months with mixed-models for repeated measures for each trial with and without chemotherapy and overall. The analysis was by intention to treat. At the time of analysis, the median follow-up was 5·7 years (IQR 3·7–6·9); treatment and follow-up of patients continue. The trials are registered with ClinicalTrials.gov , as NCT00066703 (TEXT) and NCT00066690 (SOFT). Findings Patients on tamoxifen plus OFS were more affected by hot flushes and sweats over 5 years than were those on exemestane plus OFS, although these symptoms improved. Patients on exemestane plus OFS reported more vaginal dryness, greater loss of sexual interest, and difficulties becoming aroused than did patients on tamoxifen plus OFS; these differences persisted over time. An increase in bone or joint pain was more pronounced, particularly in the short term, in patients on exemestane plus OFS than patients on tamoxifen plus OFS. Changes in global QoL indicators from baseline were small and similar between treatments over the 5 years. Interpretation Overall, from a QoL perspective, there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS. The distinct effects of the two treatments on the burden of endocrine symptoms need to be addressed with patients individually. Funding Pfizer, International Breast Cancer Study Group, and US National Cancer Institute.
BRCA1/2 genetic testing offers tremendous opportunities for prevention, diagnosis and treatment of breast and ovarian cancer. Women acquire valuable information that can help them to make informed ...decisions about their health. However, knowing one's susceptibility to developing cancer may be burdensome for several women, as this risk needs to be managed over time through a continuous dialogue with multiple healthcare professionals. We explored how communication between physicians and unaffected women carrying BRCA1/2 germline pathogenic variants was experienced by women in relation to their genetic risk. Data came from qualitative interviews conducted in Switzerland with 32 unaffected women carrying BRCA1/2 pathogenic variants and aware of their genetic status for at least 3 years. We identified three different types of message as conveyed by physicians to women: (1) a normative message, (2) an over-empowering message, and (3) a minimizing message. On one hand, we found that women are exposed to contradictory messages, often simultaneously, in their interactions with healthcare professionals during their post-genetic testing journey. On the other hand, women's reports highlighted the absence of shared decision-making in such interactions. The combination of these two findings resulted in a strong sense of disorientation, frustration, and powerlessness among participants. Healthcare professionals interacting with high cancer risk women are urged to align in favor of a both concerted and shared decision-making approach when discussing options for managing genetic risk.
The HER2 extracellular domain shed in blood (HER2
) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2
...values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy.
Quantitative assessment of plasma HER2
was performed in 133 patients at baseline; after 2-24 h; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated.
Baseline HER2
levels were stable within 24 h after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (r
= 0.39, P < 0.001) and HER2 protein expression levels (r
= 0.36, P < 0.001) but not with ER/PR status of the primary tumor. HER2
baseline levels were positively associated with the presence of visceral disease (P = 0.05) and poor patients' outcome (Cox-regression: P = 0.009). Patients with high baseline levels (> 35 ng/ml) had the worst overall survival (P = 0.03) if treated with upfront combination therapy. Conversely, patients with low HER2
baseline values (< 15 ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy (P = 0.02). Monitoring HER2
levels during the course of the trial revealed significant time (P = 0.001) and time-treatment arm interactions (P = 0.0007). Under upfront trastuzumab alone, the HER2
levels remained stable until just before disease progression. In patients responding to combination treatment HER2
levels decreased to > 20%.
Plasma HER2
levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment's modality. Monitoring HER2
levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.
Registration Number by ClinicalTrials.gov: NCT00004935, Trial number: SAKK22/99. Registered on 27 January 2003.
Premenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5–10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. ...The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy.
POSITIVE enrolled women with stage I-III HR + early breast cancer, ≤42 years, who had received 18–30 months of adjuvant ET and wished to interrupt ET for pregnancy. Treatment interruption for up to 2 years was permitted to allow pregnancy, delivery and breastfeeding, followed by ET resumption to complete the planned duration.
From 12/2014 to 12/2019, 518 women were enrolled at 116 institutions/20 countries/4 continents. At enrolment, the median age was 37 years and 74.9 % were nulliparous. Fertility preservation was used by 51.5 % of women. 93.2 % of patients had stage I/II disease, 66.0 % were node-negative, 54.7 % had breast conserving surgery, 61.9 % had received neo/adjuvant chemotherapy. Tamoxifen alone was the most prescribed ET (41.8 %), followed by tamoxifen + ovarian function suppression (OFS) (35.4 %). A greater proportion of North American women were <35 years at enrolment (42.7 %), had mastectomy (59.0 %) and received tamoxifen alone (59.8 %). More Asian women were nulliparous (81.0 %), had node-negative disease (76.2%) and received tamoxifen + OFS (56.0 %). More European women had received chemotherapy (69.3 %).
The characteristics of participants in the POSITIVE study provide insights to which patients and doctors considered it acceptable to interrupt ET to pursue pregnancy. Similarities and variations from a regional, sociodemographic, disease and treatment standpoint suggest specific sociocultural attitudes across the world.
•Fertility and pregnancy are priority concerns for young breast cancer survivors.•POSITIVE explores a transient interruption of endocrine therapy to allow conception.•Patients' characteristics highlight features considered suitable to study enrolment.•Overall, patients enrolled had a relatively high median age and low-risk disease.•Variations emerged across continents suggesting specific sociocultural attitudes.
Human epidermal growth factor receptor 2 oncogene (HER2-positive) overexpression/amplification occurs in less than 20% of breast cancers and has traditionally been associated with poor prognosis. ...Development of therapies that target HER2 has significantly improved outcomes for patients with HER2-positive advanced breast cancer (ABC). Currently available HER2-targeted agents include the monoclonal antibodies trastuzumab, pertuzumab, and margetuximab, the small-molecule inhibitors lapatinib, tucatinib, neratinib, and pyrotinib, as well as the antibody-drug conjugates trastuzumab emtansine and trastuzumab deruxtecan. Optimal sequencing of these agents in the continuum of the disease is critical to maximize treatment outcomes. The large body of clinical evidence generated over the past 2 decades aids clinicians in treatment decision-making. However, patients with HER2-positive ABC and specific disease characteristics and/or comorbidities, such as leptomeningeal disease, brain metastases, or cardiac dysfunction, are generally excluded from large randomized clinical trials, and elderly or frail patients are often underrepresented. In addition, there is great inequality in the accessibility of approved drugs across countries. This article addresses various challenging clinical situations when treating patients with HER2-positive ABC. The objective is to provide guidance to clinicians on how and when HER2-targeted therapies and additional treatments can be best implemented in routine clinical practice, on the basis of existing clinical evidence and expert opinion where needed.
HER2-targeted therapies have significantly improved outcomes for patients with ABCIdeal sequencing of regimens is key to maximize treatment benefitsNew HER2-targeted agents are used at earlier stages in BC treatmentClinical evidence for treatment of special populations with ABC is lackingApproved drugs are not accessible in all countries
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