Staging for Breast Cancer: A Nationwide Survey about Adherence to Guidelines in German Breast Centers

Introduction: The risk for metastasis at primary diagnosis of breast cancer is about 4%. The German guidelines give clear indications for when, whom and how to stage breast cancer patients. Ideally, this should be done via CAT scan of the thorax and abdomen and an additional bone scan. But daily practice shows that the way health care providers handle staging recommendations can vary. To objectify adherence to guidelines we started a nation-wide survey. Methods: Between July and September 2020 we sent out a survey via email to all certified and non certified breast centers and in addition to all Departments of Obstetrics and Gynecology in Germany. We asked for timing of staging, conditions that cause staging and the applied method. In case we did not get back any reply we sent out a reminder. Results: A total of 220 certified breast centers/28 non-certified breast center/48 Departments of Gynecology and Obstetrics who care for breast cancer patients took part in our survey. A general pre-therapeutic staging was performed in 16,4%/39,3%/66,7% of all institutions and a general post-operative staging was performed in 4,1%/0%/6,3% of each institutional type, respectively. In terms of the applied method, 75% of all certified breast centers used a CAT scan and bone scan, while 23,3% primarily use chest x-ray, ultrasound of the abdomen (27,7%) or MRI. As a potential reason for using x-ray and ultrasound the presence of a „low-risk“ breast cancer was mentioned. Summary: Although certified breast centers show the highest adherence to current guidelines, some still perform a general staging or do not use the recommended staging method. The low probability for primary metastatic breast cancer and the use of a reasonable exposure to radiation warrant a critical discussion.

Multivariable Models Based on Baseline Imaging Features and Clinicopathological Characteristics to Predict Breast Pathologic Response after Neoadjuvant Chemotherapy in Patients with Breast Cancer

Introduction Currently, the accurate evaluation and prediction of response to neoadjuvant chemotherapy (NAC) remains a great challenge. We developed several multivariate models based on baseline imaging features and clinicopathological characteristics to predict the breast pathologic complete response (pCR). Methods We retrospectively collected clinicopathological and imaging data of patients who received NAC and subsequent surgery for breast cancer at our hospital from 2014 June till 2020 September. We used mammography, ultrasound and magnetic resonance imaging (MRI) to investigate the breast tumors at baseline. Results A total of 308 patients were included and 111 patients achieved pCR. The HER2 status and Ki-67 index were significant factors for pCR on univariate analysis and in all multivariate models. Among the prediction models in this study, the ultrasound-MRI model performed the best, producing an area under curve of 0.801 (95%CI=0.749-0.852), a sensitivity of 0.797 and a specificity of 0.676. Conclusion Among the multivariable models constructed in this study, the ultrasound plus MRI model performed the best in predicting the probability of pCR after NAC. Further validation is required before it is generalized.

Expert Discussion: Hypofractionated Radiation Therapy - Standard for All Indications?

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Expert Discussion: Highlights from ABC6: Bridging the Gap and Insights in this First Virtual ABC Conference and from 10 Years ABC Consensus

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Patient-Reported Outcomes in Free-Flap Breast Reconstructive Surgery over Time (PRO-BREST)

<b><i>Introduction:</i></b> Patient-reported outcomes (PROMs) are increasingly relevant to assess surgical quality and guide decisions in breast reconstruction (BR). Satisfaction with outcomes may change as time progresses. We assessed satisfaction in patients who underwent free-flap BR in the last 12 years. <b><i>Methods:</i></b> All patients who underwent free-flap BR from 2006 to 2018 were invited to complete the validated BREAST-Q for reconstruction. The BREAST-Q comprises 6 domains covering various aspects of satisfaction. Unadjusted linear regression assessed the relationship between different domains of the BREAST-Q and time since BR. Two-sample <i>t</i> tests assessed differences in satisfaction between patients who underwent BR ≥5 years versus &#x3c;5 years prior. <b><i>Results:</i></b> Forty-three women with primary or secondary free-flap BR between 2006 and 2018 were included in the study. Most patients (<i>n</i> = 33, 76.7%) underwent DIEP flap BR. Overall satisfaction with breasts and with outcomes improved as time since BR increased (<i>p</i> = 0.031 and <i>p</i> = 0.017, respectively). Overall satisfaction with outcomes scored higher in patients with BR ≥5 years prior (≥5 years vs. &#x3c;5 years: breast score 88.6 (SD 12.5) versus 66.9 (SD 21.8); <i>p</i> = 0.005). Satisfaction with breasts and psychosocial well-being also scored higher in these patients. There was no difference in results between primary and secondary BR. Patients who underwent additional surgery (refinements) reported higher satisfaction with outcomes and abdominal well-being. <b><i>Conclusions:</i></b> PROMs concerning satisfaction with breast and with outcomes following BR improve as time since treatment progresses. This study demonstrates that time since diagnosis may be an important factor in satisfaction. It underlines the importance of long-term PROMs related to BR, to help provide patients and health care professionals in decision-making and in managing expectations related to BR.

Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis

Background: Invasive lobular carcinoma (ILC) is more likely to be bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompany by bone metastasis. Methods: We evaluated the women with bone-only metastasis of defined IDC or ILC, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson's chi-squared test was used to compare the difference of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-special survival (CSS). Results: Overall, 3647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older, lower histological grade and higher proportion of HR+/HER2- subtype. But less treatment was applied to ILC than IDC, such as surgery of the breast, radiation and chemotherapy. Compared patients with IDC, the patients with ILC showed worse OS (median OS 36 and 42 months respectively, p<0.001) and CSS (median CSS 39 and 45 months respectively, p<0.001), especially in subgroups with HR+/HER2- subtype [OS (Hazard ration: 1.501, 95% CI [1.270-1.773], p<0.001); CSS (Hazard ration: 1.529, 95% CI [1.281-1.825], p<0.001)], lower histological grade (Ⅰ-Ⅱ) [OS (Hazard ration: 1.411, 95% CI [1.184-1.683], p<0.001); CSS (Hazard ration: 1.488, 95% CI [1.235-1.791], p<0.001)] or tumor burden, such as T0-2 [OS (Hazard ration: 1.693, 95% CI [1.368-2.096], p<0.001); CSS (Hazard ration: 1.76, 95% CI [1.405-2.205], p<0.001)] and N1-2 [OS (Hazard ration: 1.451, 95% CI [1.171-1.799], p=0.001); CSS (Hazard ration: 1.488, 95% CI [1.187-1.865], p=0.001)]. Furthermore, older age, black race, unmarried status, higher tumor burden (T3-4 and N3), triple-negative subtype and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients. Conclusion: The patients with ILC have worse outcomes compared with that of IDC when bone-only metastasis occurred to them, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors (CDKs), new targeted drugs, etc.

Validation of the 21-Gene Recurrence Score Assay in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer and 0 to 3 Positive Lymph Nodes – Risk Pattern and Outcomes on a Community Level

Introduction The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX) in patients with 0-3 lymph nodes in a high volume community hospital. Methods Patients with non-metastatic HR+/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX testing were included in this retrospective study. The distribution of clinico-pathologic characteristics, recurrence score (RS) risk and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease free survival (DFS) and overall survival (OS) were estimated. Results From 2012 to2017 ODX was consecutively performed in 575 (16.4%) of 3492 women with HR+/ HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had a RS of 0 to 25 and 112 (20.3%) had a RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5y-DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p= 0.101) or OS (97.2% vs. 96.0%; p= 0.737) for patients with a RS 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions The results of the study confirm the observations from randomized studies on the use of the ODX in a real world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR+/HER2- breast cancer with 0-3 positive lymph nodes and RS<25.

Does Routine Follow-Up after Patients Have Completed Adjuvant Therapy for Early-Stage Breast Cancer at a Cancer Center Improve Prognosis?

<b><i>Introduction:</i></b> This study aimed to assess whether follow-up of patients with operative breast cancer at cancer centres (CCs) improved prognosis compared with follow-up by family physicians (FPs). <b><i>Methods:</i></b> The study included 254 patients who relapsed within 7 years from the first postoperative period. The patients were divided into two groups according to the follow-up facility: the CC and FP groups (the follow-up of patients was structured in the same way between FPs and CCs). There are 146 and 108 cases of recurrence in the CC and FP groups, respectively. The analysis targets of the two groups were determined using the propensity matching method based on the following 7 factors: oestrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, St. Gallen category, menopausal status, surgical procedure, and receipt of postoperative chemotherapy at the time of surgery. Overall survival (OS) in both groups was analysed using the Kaplan-Meier method and compared using the log-rank test. <b><i>Results:</i></b> Overall, 97 patients each in the CC and FP groups who relapsed were analysed using the propensity matching method. The median recurrence-free survival periods were 1,676 and 994 days in the FP and CC groups, respectively, and were significantly longer in the FP group. However, the median OS starting from the day of surgery was 3,424 and 2,794 days in the FP and CC groups, respectively, with no significant difference. <b><i>Conclusion:</i></b> This study revealed that regular follow-up at CCs did not improve survival compared with regular follow-up by FPs.

Second-Degree Type 2 Atrioventricular Block Requiring Permanent Cardiac Pacing in Patients on CDK4/6 Inhibitors: Report of Two Cases

<b><i>Introduction:</i></b> A wide spectrum of cardiovascular (CV) toxicity is associated with anticancer treatment, and nearly all chemotherapeutic agents can elicit CV toxicity. Inhibitors of cyclin-dependent kinases 4/6 (CDK4/6Is) have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC). CV side effects are uncommon with CDK4/6Is and only include QT prolongation, with a low incidence rate. <b><i>Case Presentation:</i></b> This paper describes 2 cases of new-onset second-degree type 2 atrioventricular (AV) blocks requiring permanent cardiac pacing involving 2 women with MBC receiving ribociclib or abemaciclib. Both our patients had no known history or risk factors of cardiac disease and a normal 12-lead resting electrocardiogram (ECG) when diagnosed with breast adenocarcinoma. Both patients have been subjected to surveillance for cardiotoxicity with serial ECG and echocardiography. No left ventricular dysfunction or arrhythmia was found during the follow-up, and cardiac biomarkers were normal. <b><i>Conclusion:</i></b> To our knowledge, these are the first cases reported in the literature of new-onset advanced AV blocks in patients under treatment with CDK4/6Is, suggesting the clinical relevance of a more frequent ECG monitoring, besides the QT interval, in these patients.