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.
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 < 0.001). Preoperative histological grading lacked prognostic power. When comparing the patient characteristics of the subgroups, we found significant difference in the following characteristics: cT, ypT, ypN, pCR and chemotherapy regimens (p < 0.001). There was no difference in OS when comparing the two subgroups. Pathological complete response (pCR) rates had a significant impact on OS and disease-free survival (DFS) in HER2+ and triple negative subtypes (p = 0.03). In multivariate analysis, high proliferation index (> 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.
The legalisation of assisted suicide is one of the most debated topics in the field of medical ethics worldwide. In countries in which assisted suicide is not legal, public discussions about its ...approval also encompass considerations of the long-term consequences that such legalisation would bring, for example, how many people will use this option, from what conditions would they be suffering, would there be differences between male and female assisted suicide and which developments and trends could be expected if there were to be a marked increase of cases of assisted suicide over time?
In order to answer these questions, we present the development of assisted suicide in Switzerland over a 20-year period (1999-2018; 8738 cases) using data from the Swiss Federal Statistical Office.
During the observation period, the number of assisted suicides rose significantly: when four 5-year periods (1999-2003, 2004-2008, 2009-2013, 2014-2018) were analysed, the number of assisted suicide cases doubled over each period compared with the preceding one (Χ = 206.7, 270.4 and 897.4; p <0.001). The percentage of assisted suicides among all deaths rose from 0.2% (1999-2003; n = 582) to 1.5% (2014-2018: n = 4820). The majority of people who chose assisted suicide were elderly, with increasing age over time (median age in 1999-2003: 74.5 years vs 2014-2018: 80 years), and with a predominance of women (57.2% vs 42.8%). The most common underlying condition for assisted suicide was cancer (n = 3580, 41.0% of all assisted suicides). Over time, assisted suicide increased similarly for all underlying conditions; however, the proportion in each disease group remained unchanged.
It is a matter of one's viewpoint whether the rise of assisted suicide cases should be considered alarming or not. These figures reflect an interesting social development but still do not appear to represent a mass phenomenon.
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.
Conclusion
Our results indicate that prognostic information in HER2 positive breast cancer also depends on the methodology of how positivity was determined. In our cohort, FISH was superior to IHC based positive HER2 status.
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.
Objectives:
To evaluate the most recent developments of medical aid in dying (MAID) in Switzerland and to test the reliability of reporting this phenomenon in cause of death statistics.
Methods:
By ...reviewing the MAID cases between 2018 and 2020, we compared the diseases and conditions underlying MAID reported by the ICD-based statistics provided by the Swiss Federal Statistical Office (FSO,
n
= 3,623) and those provided by the largest right-to-die organization EXIT (
n
= 2,680).
Results:
EXIT reported the motivations underlying the desire for death in a mixture of disease-specific and symptom-oriented categories; the latter including, for example, multimorbidity (26% of cases), and chronic pain (8%). Symptom-oriented categories were not included in the ICD-based FSO statistics. This led to the fact that the distribution of the diseases/conditions underlying MAID differed in 30%–40% of cases between both statistics.
Conclusion:
In order to reliably follow developments and trends in MAID, the diseases/conditions underlying the wish to die must be accurately recorded. Current methods of data collection using the ICD classification do not capture this information thoroughly (“MAID gap”). Newly created ICD codes for MAID must include both disease-specific and symptom-oriented categories.
Background
Ultrasound (US)-guided breast biopsy is a routine diagnostic method used to correlate imaging finding to a histological diagnosis which is still the gold standard in preoperative ...diagnostics. The accuracy of US-guided breast biopsies relies on a precise radiologic-histopathologic correlation, which is discussed amongst an interdisciplinary team of gynecologists, radiologists and pathologists. However, false-negative or non-diagnostic biopsy results occur. Hence, a thorough and honest discussion to clarify the reason for discrepancies and to decide the next diagnostic step between specialists of the different disciplines is warranted. In this retrospective study, we analyzed discrepant findings between imaging and pathology results on preoperative breast biopsies.
Methods
Core and vacuum-assisted breast biopsies from 232 patients were included in this study. Inclusion criteria were (1) non-diagnostic (B1) category on histology independent from imaging category and (2) histological benign (B2) category with a BIRADS 5 (Breast Imaging Reporting and Data System) rating on imaging. Histological diagnoses were retrieved from all cases. Follow-up data were available in most cases.
Results
138 biopsies were classified as B1, 94 biopsies as B2 category. 51 of 138 B1 cases (37%) underwent re-biopsy. Re-biopsy found malignancy (B5) in 19 of 51 cases, and B3/4 (premalignant) lesions in 3 of 51 cases. All B2 cases underwent second-look imaging-diagnosis, in 57 of 94 cases (66%) consecutive direct surgery or re-biopsy. Of these, malignancy was diagnosed histologically in 26 of 57 cases (45.6%).
Conclusion
Determining imaging-pathology concordance after US-guided breast biopsy is essential. Discrepant cases and further diagnostic steps need to be discussed with an interdisciplinary approach.
Background
We tested the hypothesis of supporters of assisted dying that assisted suicide (AS) might be able to prevent cases of conventional suicide (CS).
Methods
By using data from the Federal ...Statistical Office, we analyzed the long‐term development of 30,756 self‐initiated deaths in Switzerland over a 20‐year period (1999–2018; CS: n = 22,018, AS: n = 8738), focusing on people suffering from cancer who died from AS or CS.
Results
While cancer was the most often listed principal disease for AS (n = 3580, 41.0% of AS cases), cancer was listed in only a small minority of CS cases (n = 832, 3.8% of CS cases). There was a significant increase in the absolute number of cancer‐associated AS cases: comparing four 5‐year periods, there was approximately a doubling of cases every 5 years (1999–2003: n = 228 vs.2004–2008: n = 474, +108% compared with the previous period; 2009–2013: n = 920, +94%; 2014–2018: n = 1958, +113%). The ratio of cancer‐associated AS in relationship with all cancer‐associated deaths increased over time to 2.3% in the last observation period (2014–2018). In parallel, the numbers of cancer‐associated CS showed a downward trend only at the beginning of the observation period (1999–2003, n = 240 vs. 2004–2008, n = 199, −17%). Thereafter, the number of cases remained stable in the subsequent 5‐year period (2009–2013, n = 187, −6%), and increased again toward the most recent period (2014–2018, n = 206, +10%).
Conclusion
The assumption that, with the increasingly accessible option of AS for patients with cancer, CS suicide will become “superfluous” cannot be confirmed. There are strong reasons indicating that situations and circumstances of cancer‐associated CS are different from those for cancer‐associated AS.
In order to test the hypothesis of supporters of assisted suicide (AS) that legalization of this procedure might be able to prevent cases of conventional suicide (CS), we tested the long‐term development of 30,756 self‐initiated deaths in Switzerland over a 20‐year period (1999–2018; CS: n = 22,018, AS: n = 8738), focusing on people suffering from cancer who died from AS or CS. While cancer was the most often listed principal disease for AS (n = 3580, 41.0% of AS cases), cancer was listed in only a small minority of CS cases (n = 832, 3.8% of CS cases). There was a significant increase in the absolute number of cancer‐associated AS cases in that there was approximately a doubling of cases every 5 years (1999–2003: n = 228, 2004–2008: n = 474, 2009–2013: n = 920, 2014–2018: n = 1958). In parallel, the numbers of cancer‐associated CS remained comparatively stable (1999–2003: n = 240, 2004–2008: n = 199, 2009–2013: n = 187, 2014–2018, n = 206). The assumption that, with the increasingly accessible option of AS for patients with cancer, CS suicide will become “superfluous” cannot be confirmed. There are strong reasons indicating that situations and circumstances of cancer‐associated CS are different from those for cancer‐associated AS.
Purpose
When ipsilateral breast-tumor recurrence (IBTR) following breast-conserving surgery (BCS) occurs, the cure of a potentially life-threatening disease is the main goal. If, however, this is ...diagnosed early, prognosis is still good and patient-reported outcomes become more important. Despite the fact that many patients would prefer a further BCS, international breast cancer guidelines still recommend mastectomy, mainly because previous radiation implies limited options. Our comparative study evaluates the long-term quality-of-life and outcome in patients with IBTR who received BCS plus intraoperative radiotherapy (IORT) versus mastectomy.
Methods
Patients with IBTR were retrospectively divided into three groups according to the local treatment: group 1 (
n
= 26) was treated with BCS + IORT; group 2 (
n
= 35) received a standard mastectomy; group 3 (
n
= 52) had a mastectomy with subsequent reconstruction. Outcomes were analyzed after a mean follow-up of 5 years after IBTR. Quality-of-life was evaluated by the validated questionnaire BREAST-Q in 50 patients who fulfilled the inclusion criteria.
Results
Quality-of-life scores varied within the groups, ranging from 51.4 to 91.3 (out of 100 points). We observed satisfactory scores in all items, with no statistical difference within the groups. Disease-free survival of all groups did not statistically differ, and overall mortality was very low (0.9%). The postinterventional complication rate was lower after BCS (19.2% versus 34.3% after mastectomy and 30.8% after mastectomy with reconstruction).
Conclusion
For patients with previous surgery and radiation who demand a second BCS in the recurrent situation, this surgical technique can be offered in combination with IORT. Our long-term results imply oncological safety, lower complication rate, and good patient satisfaction.
Zusammenfassung
Über die häufigste Krebserkrankung der Frau, das Mammakarzinom, sind heute multiple beinflussbare und nichtbeeinflussbare Risikofaktoren bekannt. Es ist entscheidend, das individuelle ...Risiko zu kennen, um durch gezielte Massnahmen ebensolches senken zu können. Dieser Übersichtsartikel zeigt die Gewichtung der einzelnen Risikofaktoren als Basis für eine Beratung im ärztlichen Alltag. Präventive Massnahmen sind beispielsweise körperliche Aktivität, Gewichtsreduktion und Senkung des Alkoholkonsums. In bestimmten Konstellationen ist eine genetische Testung sinnvoll; bei sehr hohem Risiko, z. B. durch eine pathogene BRCA-Mutation, kommen auch risikoreduzierende Mastektomien infrage.
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