Metastatic Breast Cancer as a Chronic Disease: Evidence-Based Data on a Theoretical Concept

Background: We challenge the concept of metastatic breast cancer (MBC) as a chronic disease. Methods: We analyzed an unselected cohort of 367 patients who were diagnosed with MBC over a 22-year period (1990–2011). Results: In order to create a “chronic disease subgroup”, we separated those patients from the entire cohort in whom systemic therapy was not applied after the diagnosis of MBC (n = 53; 14.4%). Three hundred fourteen patients (85.6%) comprised the “chronic disease subgroup”. The vast majority of those patients (89.8%) died of progressive disease after a median metastatic disease survival (MDS) of 25 months. Twenty patients (6.4%) died of non-MBC-related causes (MDS 38.5 months). Approximately 1 in 4 patients (26.8%) died within the first year after the MBC diagnosis. The 3- and 5-year MDS rates were 35.4 and 16.2%, respectively. Only 12 patients (3.8%) were exceptional survivors (MDS >10 years). Conclusion: The term “chronic disease” might be appropriate in selected MBC cases, bringing MBC into alignment with “classical” chronic diseases such as diabetes and hypertension. However, most cases display fundamental differences with regard to temporal progression and above all the case fatality rate. More than 90% of patients in the “chronic disease subgroup” died of the disease with a MDS of 2–3 years (even those who underwent systemic palliative therapies). Doctors and patients might understand the term “chronic disease” differently. The term must be used sparingly and explained carefully in order to create a common level of communication based on a shared understanding which avoids awakening false hopes and fostering misleading expectations

The role of trust in the acceptance of adjuvant endocrine therapy in breast cancer patients

Objective: Despite adjuvant endocrine therapy (AET) considerably reducing mortality and recurrence in hormonal receptor-positive (HR+) breast cancer (BC) patients, acceptance of AET remains an issue. The reasoning behind the lack of acceptance is complex and multifactorial, and some associated risk factors have been previously analyzed. Our study aims to assess women's beliefs and concerns toward AET and women's trust in the treating physician, focusing on determining the importance of these factors in the acceptance of AET. Methods: Out of n = 539, n = 269 women with HR + BC participated in a cross-sectional online survey. The main study variables were AET necessity beliefs and concerns (Beliefs about Medicines Questionnaire) and the trust in treating physicians. A binary hierarchical logistic regression was applied to predict AET acceptance. Results: We did not observe a meaningful mean difference in the necessity beliefs between women who accepted versus refused AET by the time of study conduct. Women with ongoing AET intake indicated significantly higher trust in their treating physician (d = 0.57) and have lower concerns (d = -1.65) regarding AET than women who had declined or discontinued AET prematurely. Results of the logistic regression demonstrated that after adjusting for clinical factors (e.g., prognosis, age), higher trust and lower concerns significantly increased the likelihood of accepting AET treatment. Conclusions: Our results demonstrate the importance of discussing potential concerns regarding AET and establishing a trustful patient-physician relationship, which outweighs non-modifiable factors such as cancer prognosis

Clinical Imaging of the Heterogeneous Group of Triple-negative Breast Cancer

BACKGROUND/AIM Triple-negative breast cancer (TNBC) can be divided into subtypes of basal-like (BL), mesenchymal-like (ML), luminal androgen receptor (LAR), and immunomodulatory (IM). The aim of our study was to assess whether there are distinct radiologic features within the different TNBC subtypes and whether this has potential clinical impact. PATIENTS AND METHODS Imaging pictures of 135 patients with TNBC were re-evaluated. TNBC subtyping was performed on asservated tumor tissue using a panel of antibodies. RESULTS Mammographic margins of LAR-TNBC were more often spiculated (24.3% versus 0-4.1%). BL-TNBC presented more frequent a mass without calcification in mammogram than other subtypes (71.4% versus 48.6-57.9%). In ultrasound, ML and LAR were described more often with smooth borders. CONCLUSION The histopathological subtype of TNBC influences its presentation in ultrasound and mammogram. This can reflect a different growth pattern of the subtypes and may have an impact on the early diagnosis of TNBC

Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions)

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH

Targeted Therapy in HR+ HER2− Metastatic Breast Cancer: Current Clinical Trials and Their Implications for CDK4/6 Inhibitor Therapy and beyond Treatment Options

A metastatic state of breast cancer (MBC) affects hundreds of thousands of women worldwide. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) MBC, cyclin-dependent kinase (CDK)4/6 inhibitors can improve the progression-free survival (PFS), as well as the overall survival (OS), in selected patients and have been established as first- and second-line therapies. However, as MBC remains uncurable, resistance to CDK4/6 inhibitors occurs and requires alternative treatment approaches. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. This review provides a summary and update on the clinical relevance, patient selection, ongoing trials of CDK4/6 inhibitors, and further targeted therapy options. It focuses on clinical aspects and practicability, as well as adverse events and patient-reported outcomes

Breastfeeding in women having experienced childhood sexual abuse

BACKGROUND Childhood sexual abuse (CSA) can have a serious effect on general and obstetric health. Breastfeeding includes several triggers for memories of abuse experiences, which will likely influence decisions about breastfeeding and its implementation in daily life. This is important since breastfeeding improves maternal well-being and bonding with the child. Research aim: As breastfeeding strongly influences the long-term health of children, we investigated experiences with breastfeeding in women with a history of CSA. METHODS Data on breastfeeding were collected within a research project designed to compare labor and delivery experiences in women with a history of CSA to women without such antecedents. Data from 85 women having experienced CSA and 170 controls pair-matched for maternal age, children's age, and nationality were evaluated. The clinical record of pregnancy and a self-administered questionnaire were used to collect data. RESULTS Although the prevalence of breastfeeding was similar in women with and without CSA experiences (96.5% vs. 90.6%), women exposed to CSA more often described complications associated with breastfeeding (77.7% vs. 67.1%, p = .08). Mastitis (49.4% vs. 27.6%, p < .01) and pain (29.4% vs. 18.8%, p = .15) were reported significantly more often by women after CSA. For 20% of women after CSA, breastfeeding was a trigger for memories of CSA. Furthermore, 58% of women with CSA reported dissociation when breastfeeding. CONCLUSION In addition to the growing list of potential health consequences of CSA experience, this experience seems to be associated with an increased number of problems when breastfeeding. However, most women with a history of CSA intend to breastfeed despite particular challenges related to CSA. A support protocol tailored to the specific needs of these women during pregnancy and the lactation period may help to improve breastfeeding and the early mother-child relationship

Biomarker dynamics and prognosis in breast cancer after neoadjuvant chemotherapy

Breast cancer is a biologically diverse disease with treatment modalities selected based on tumor stage and tumor biology. Distinct intrinsic subtypes and surrogate biomarker profiles play a major role for therapeutic decisions. Response rates to systemic and local treatments as well as the interaction with epidemiological risk factors have been validated in clinical trials and translational studies. This retrospective study addresses the question how biomarker profiles and treatment modalities in the neoadjuvant chemotherapy setting have changed during the past 15 years and what prognostic impact these changes implicate. 342 female breast cancer stage I-IV patients receiving neoadjuvant chemotherapy between 2003 and 2017 were analyzed. Overall survival (OS) was correlated with preoperative clinical stage, postoperative pathological stage, treatment modalities and tumor biology before and after chemotherapy. Two subgroups were separated using an arbitrary cut-off year at 2009/2010, due to 2010 when platinum containing regimens were first administered. Median follow-up was 54 months. 57 (17%) patients died; recurrences occurred in 103 of 342 (30%) patients. Nodal stage and intrinsic subtypes (pre- and postoperative) significantly correlated with OS (p  30%), clinical metastatic stage and pathological tumor stage had prognostic impact on OS (p < 0.001, p = 0.0001, p = 0.002). Clinico-pathological factors and distinct therapy regiments especially in triple negative and HER2+ subtypes have prognostic impact on pCR, OS and DFS after neoadjuvant chemotherapy

Differential prognostic value of positive HER2 status determined by immunohistochemistry or fluorescence in situ hybridization in breast cancer

Purpose Human epidermal growth factor-receptor-2 (HER2) is a membrane-tyrosine-kinase that is amplified/overexpressed up to 20% in breast cancer. HER2 positive status is associated with faster disease progression, higher metastatic potential, and shorter disease-free/overall survival and also has emerged as an important therapeutic target in breast cancer. HER2 status can be determined by in-situ-hybridization (ISH) or immunohistochemistry (IHC). Although the concordance rate between ISH and IHC is well-known, the prognostic power of both technologies if tested in parallel on the same tumor has not been studied extensively. Methods In this study we retrospectively analyzed a large HER2 positive breast cancer cohort tested both with fluorescence labeled ISH (FISH) and IHC in parallel on each case. We stratified HER2 positive results by FISH and IHC with long-term overall survival, 5-year survival and metastases/recurrence rates. Positive HER2 status both FISH and IHC was available in 364 patients. Results The number of HER2 FISH-positive and FISH-negative patients was 342 and 22, respectively. The number of HER2 IHC 0/1 + , IHC 2 + , and IHC 3 + patients was 12, 42, and 310, respectively. Among the patients with IHC 3 + status, 288 were FISH-positive and 22 FISH-negative. HER2 status determined by FISH correlated with clinical outcomes (overall survival and with metastases/recurrence, p = 0.036, p = 0.039), whereas HER2 status determined by IHC did not