Trastuzumab and survival of patients with metastatic breast cancer.

INTRODUCTION: Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. METHODS: All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001-2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan-Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. RESULTS: Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3-4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58-2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan-Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3-4.6). CONCLUSION: Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without trastuzumab warrants further research. Survival is best in triple-positive metastatic breast cancer. This will effect counseling at the time of first diagnosis of metastatic breast cancer.

Impact of breast cancer subtypes and patterns of metastasis on outcome.

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006-2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2-, G1/2), luminal B/Her2 negative (ER+, Her2-, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER-, Her2+), and triple negative (ER-, PR-, Her2-) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive subtypes.

No Survival Benefit for Patients with Treatment in Certified Breast Centers-A Population-based Evaluation of German Cancer Registry Data.

Much time and money has been spent on the establishment and preservation of certified breast centers (CBCs), but up to now there is almost no evidence for whether certification results in an improved outcome for breast cancer patients. The aim of this evaluation was to assess, whether the certification of specialized units had any influence on their patients' outcomes and if a survival difference between CBC patients and non-CBC patients can be shown. This population-based analysis included cancer registry data from 32,789 operated breast cancer patients with no prior cancer diagnosis and with active follow-up. They were diagnosed between 2004 and 2010 in four different regions in Germany. Survival was investigated using the Kaplan-Meier method and multivariate Cox regression analysis. A survival difference was found neither between patients with treatment before and after certification of specialized units nor between CBC patients and non-CBC patients aged up to 75 years. Only for patients older than 75 years, an improved survival could be seen for CBC patients (adjusted hazard ratio 0.77; 95% confidence interval 0.68-0.87). The improved survival of elderly CBC patients is most likely caused by selection effects concerning health status differences and not by processes attributable to certification. Thus, this study found that as of yet, certification has not influenced survival of breast cancer patients.

Recommendation and Acceptance of Counselling for Familial Cancer Risk in Newly Diagnosed Breast Cancer Cases.

Background: In clinical routine, not every patient who is offered genetic counselling and diagnostics in order to investigate a familial cancer risk predisposition opts for it. Little is known about acceptance of counselling and testing in newly diagnosed breast cancer cases in Germany. Methods: All primary breast cancer cases and patients with DCIS (ductal carcinoma in situ) treated at the University Hospital of Dresden between 2016 and 2019 were included. The number of tumor board recommendations for genetic counselling on the basis of the GC-HBOC risk criteria was recorded. Acceptance was analyzed by number of cases with counselling in the GC-HBOC-Center Dresden. Results: Of 996 primary breast cancer and DCIS cases, 262 (26.3%) were eligible for genetic counselling. Recommendation for genetic counselling was accepted by 64.1% (168/262). Of these 90.5% (152/168) opted for molecular genetic analysis. The acceptance rate for counselling increased between 2016 and 2019 from 58.3 to 72.6%. Altogether, 20.4% (31/152) patients were found to carry a pathogenic variant in the breast cancer genes BRCA1 or BRCA2. Conclusion: Acceptance of recommendation is increasing as clinical consequences augment. Optimization in providing information about hereditary cancer risk and in accessibility of counselling and testing is required to further improve acceptance of recommendation.

A 10-year analysis of primary cutaneous malignant melanoma with sentinel lymph node biopsy and long-term follow-up.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important tool for accurate staging of patients with melanoma. There is an ongoing debate whether the procedure provides therapeutic benefits or not. OBJECTIVE: We wanted to analyze 10-year data from an academic teaching hospital. PATIENTS AND METHODS: During 1999-2009, 977 patients with early cutaneous melanoma have been treated. Of these, 419 patients had tumors ≥ 1 mm thickness. Patients with head and neck tumors were excluded, leaving 364 patients (202 men and 162 women). SLNB was not performed in 163 patients but was performed in 201 patients. For correction of bias, tumors >4 mm thickness were excluded from further statistical analysis. RESULTS: The detection rate of SLN was 94.4%. False negative SLN were observed in 8.9%. Adverse effects occurred in 5.5%. The rate of positive SLNB was 16.4% and lymph node involvement 20%. Patients undergoing SLNB had a lower relapse rate (10.6% vs. 33.3%; P < 0.001). The most important finding is an almost 50% lower total death rate and melanoma-related death rate in the SLNB subgroup (P < 0.001 for both). CONCLUSIONS: Sentinel lymph node biopsy is an accurate instrument for melanoma staging to detect occult regional lymph node involvement. Data suggest a positive effect on relapse-free survival. The observation of improved long-term survival needs validation in prospective multicenter trials. The limitations of this study were that it was a single center retrospective analysis.