The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry

Breast Cancer Research and Treatment - The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the main parameters in guiding systemic treatment choices in breast cancer,...     

A review of the treatment of endocrine responsive metastatic breast cancer in postmenopausal women

Endocrine therapy is the corner stone treatment for postmenopausal women with hormone receptor-positive metastatic breast cancer (MBC). Besides tamoxifen and many older agents, recently developed endocrine agents for the treatment of MBC include the third generation aromatase inhibitors (AI) – anastrozole, exemestane, letrozole – and the pure oestrogen receptor antagonist fulvestrant. As treatment of breast cancer evolves, both tamoxifen and the AIs are being increasingly used in the adjuvant setting. As such, a significant proportion of patients with hormone receptor-positive MBC will have previously received tamoxifen, an AI or both, as adjuvant treatment. This has changed the metastatic landscape and has an impact on treatment choices for patients with hormone receptor-positive MBC. In this review, we evaluate the available evidence supporting the use of endocrine therapy for the treatment of hormone receptor-positive MBC. Additionally, we consider the effect of prior adjuvant therapy on treatment choice in the metastatic setting and the optimal treatment sequence. Finally, we discuss endocrine-responsive HER2 positive tumours and the ongoing research initiatives which aim to improve outcomes for patients with MBC.     

Prognosis following local recurrence after breast conserving treatment in young women with early breast cancer

Background

Few studies have focussed on the prognosis of young women with local recurrence (LR) after breast-conserving therapy and the factors that can be used to predict their prognosis.

Methods

We studied the outcome and related prognostic factors in 124 patients with an isolated local recurrence in the breast following breast-conserving surgery and radiotherapy for early stage breast cancer diagnosed at the age of 40 years or younger.

Results

The median follow-up of the patients after diagnosis of LR was 7.0 years. At 10 years from the date of salvage treatment, the overall survival rate was 73% (95% CI, 63–83), the distant recurrence-free survival rate was 61% (95% CI, 53–73), and the local control rate (i.e. survival without subsequent LR or local progression) was 95% (95% CI, 91–99). In the multivariate analysis, the risk of distant metastases also tended to be higher for patients with LR occurring within 5 years after BCT, as compared to patients with LR more than 5 years after BCT (Hazard ratio [HR], 1.89; p = 0.09). A worse distant recurrence-free survival was also observed for patients with a LR measuring more than 2 cm in diameter, compared to those with a LR of 2 cm or smaller (HR, 2.88; p = 0.007), and for patients with a LR causing symptoms or suspicious findings at clinical breast examination, compared to those with a LR detected by breast imaging only (HR 3.70; p = 0.03).

Conclusions

These results suggest that early detection of LR after BCT in young women can improve treatment outcome.     

Variation in management of early breast cancer in the Netherlands, 2003–2006

BackgroundTo describe variation in staging and primary treatment by hospital characteristics including type and volume and region in patients with early breast cancer (BC) in the Netherlands, 2003–2006 after completion of national guidelines in 2002.MethodsAll patients newly diagnosed with invasive BC in 2003–2006 and recorded in the Netherlands Cancer Registry were included (n = 51 354). Multivariable logistic regression analyses examined the influence of patient and hospital characteristics, also by region, on type of breast surgery, axillary lymph node dissection (ALND), sentinel node procedure (SNP), and adjuvant irradiation and/or systemic treatment.ResultsPatients <40 years more often underwent breast conserving surgery (BCS) in general hospitals (OR 1.4 (95%CI 1.1–1.5)) than in teaching and academic hospitals, whereas patients of 40–69 years less often received BCS in an academic hospital (OR 0.9 (95%CI 0.8–1.0)) than in teaching hospitals. Patients with pT1-2N0 cancer more often underwent primary ALND in a general hospital than in a larger teaching or academic hospital. Type of hospital did not seem to affect utilization of adjuvant systemic therapy, but patient age and tumour size and grade did. Over time, patients more often received SNP, BCS, and adjuvant systemic therapy, primary ALND being on the decline, but with substantial regional variation between geographic regions.ConclusionWith detailed evidence-based national guidelines since 2002 the considerable regional and hospital variation in staging procedures and primary treatment among newly diagnosed patients with early breast cancer in the Netherlands decreased markedly, suggesting the presence of late adaptors rather than specific hospital characteristics.     

Febrile neutropenia: highlighting the role of prophylactic antibiotics and granulocyte colony-stimulating factor during standard dose chemotherapy for solid tumors

The prevention of chemotherapy-induced febrile neutropenia is important as it reduces hospitalization and is likely to improve quality of life. Several prophylactic strategies are available, although their use in patients with an anticipated short duration of neutropenia is controversial and not recommended. This paper presents the results of a review of the literature on the efficacy and cost-effectiveness of prophylactic antibiotics and/or granulocyte colony-stimulating factor, and also discusses the recommendations in current guidelines in view of recent publications. Both primary prophylactic granulocyte colony-stimulating factor and prophylactic antibiotics reduce the risk of febrile neutropenia considerably, and the addition of prophylactic granulocyte colony-stimulating factor to antibiotics is even more effective. As antibiotics, however, give rise to antimicrobial resistance and granulocyte colony-stimulating factor is expensive, tailoring of prophylaxis is clearly needed. This will increase the absolute clinical and economical benefits of prophylaxis. Patient-related, treatment-related and disease-related factors enhancing the risk of febrile neutropenia are discussed, including the, underrated, high risk of febrile neutropenia specifically in the first cycles of chemotherapy. Half of the patients developing febrile neutropenia during treatment do so in the first cycle of chemotherapy, which favors primary prophylaxis. The efficacy of secondary prophylaxis is not well documented. Finally, new interesting agents in the treatment and supportive care of solid tumors have become available, and these are discussed in relation to the incidence and prevention of febrile neutropenia.     

High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer

Summary Variants of survivin with differing subcellular localizations might mediate the different functions of survivin, i.e. cell-cycle regulation and apoptosis inhibition. Highly proliferative tumors are more sensitive to chemotherapy, whereas apoptosis resistant cells would be refractory to endocrine therapy. Possibly, this explains incongruent data on the association of survivin with prognosis in breast cancer. Survivin levels were measured using ELISA in 800 × g pellets and 100,000 × g supernatants of breast cancer tissues from patients that were treated with either chemotherapy or endocrine therapy for advanced disease. These fractions might be enriched with nuclear or cytoplasmatic located survivin variants. Survivin levels were associated with tumors with poor prognostic clinical characteristics. For the patients treated with endocrine therapy, the patients with high survivin levels exhibited a significantly shorter progression free survival (PFS) than those who had low levels (pellet survivin Hazard Ratio (HR)=2.74, 95% Confidence Interval (CI)=1.31–5.72, p=0.008 and median PFS 5.8 versus 8.6 months, p=0.006, log-rank; cytosolic survivin HR=3.03, 95% CI=1.45–6.35, p=0.003). In contrast, for patients treated with chemotherapy, those with high cytosolic survivin had a significantly longer PFS than those with low levels (median PFS of 6.2 months, versus 4.7 months for patients with low cytosolic concentrations, p=0.024, log-rank). Thus, high levels of survivin are mainly related with a poor response to endocrine therapy, but a good response to chemotherapy. This phenomenon might be related to the different functions of survivin.     

EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (>or=65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10-20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.     

Direct Medical Costs of Advanced Breast Cancer Treatment: A Real-World Study in the Southeast of The Netherlands

ObjectivesPolicy makers increasingly seek to complement data from clinical trials with information from routine care. This study aims to provide a detailed account of the hospital resource use and associated costs of patients with advanced breast cancer in The Netherlands.MethodsData from 597 patients with advanced breast cancer, diagnosed between 2010 and 2014, were retrieved from the Southeast Netherlands Advanced Breast Cancer Registry. Database lock for this study was in October 2017. We report the observed hospital costs for different resource categories and the lifetime costs per patient, adjusted for censoring using Lin’s method. The relationship between patients’ characteristics and costs was studied using multivariable regression.ResultsThe average (SE) lifetime hospital costs of patients with advanced breast cancer were €52 709 (405). Costs differed considerably between patient subgroups, ranging from €29 803 for patients with a triple-negative subtype to €92 272 for patients with hormone receptor positive and human epidermal growth factor receptor 2 positive cancer. Apart from the cancer subtype, several other factors, including age and survival time, were independently associated with patient lifetime costs. Overall, a large share of costs was attributed to systemic therapies (56%), predominantly to a few expensive agents, such as trastuzumab (15%), everolimus (10%), and bevacizumab (9%), as well as to inpatient hospital days (20%).ConclusionsThis real-world study shows the high degree of variability in hospital resource use and associated costs in advanced breast cancer care. The presented resource use and costs data provide researchers and policy makers with key figures for economic evaluations and budget impact analyses.