The primary aim of treatment of a patient who has developed metastatic disease is palliation. The objectives of the current study are to describe and quantify the clinical management of women with ...metastatic breast cancer from the diagnosis of metastatic disease until death and to analyze differences between age groups.
Data were collected from the medical files of all patients (n = 116) who had died after December 31, 1999, after a diagnosis of metastatic breast cancer in two teaching hospitals in the south of the Netherlands.
Of the 116 patients included in our study, 10 (9%) already had metastatic disease at diagnosis and 106 developed distant disease after the diagnosis of localized breast cancer. Before they died, 70% of the 116 patients developed metastases in one or more bones, 50% in the lung and/or pleura, 50% in the abdominal viscera, 23% in the central nervous system, and 19% in the skin. Patients younger than 50 years were much more likely to develop metastases in the central nervous system than patients 50 years and older. Seventy-seven (66%) of the 116 patients with metastatic breast cancer received chemotherapy. This proportion decreased with age (p = 0.005), as did the number of schemes per patient. Together, they received 132 chemotherapy schemes, of which 35 (27%) resulted in partial remission or stabilization of the disease process. Ninety-eight patients (84%) received hormonal treatment. This proportion did not differ between the three age groups. Together, they received 216 hormonal treatments, 38 (16%) of which resulted in partial remission or stabilization of the disease process. Seventy-nine patients (68%) received palliative radiotherapy. This proportion decreased with age (p = 0.03). Together, they underwent 216 courses, 176 (77%) of which resulted in relief of the complaints.
Patients aged 70 years and older are less likely to receive chemotherapy or radiotherapy. Part of this difference could be explained by their shorter survival time after the diagnosis of metastatic disease and their lower risk of developing brain and bone metastases. However, more research is needed to understand the age-related differences in the treatment of metastatic breast cancer, and especially how comorbidity and frailty limit therapeutic choices.
Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally ...treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.
Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.
The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.
NCT01392586.
The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2–3 years of tamoxifen. This planned ...side‐study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate‐use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T‐scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6‐ and 3‐year group respectively (p = 0.18), during follow‐up. Only two patients (3‐year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6‐ and 3‐year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD‐change during anastrozole in the lumbar spine showed a T‐score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole‐use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation.
What's new?
Loss of bone mineral density (BMD) is a side effect of aromatase inhibitor treatment, a class of drugs that stops estrogen production in postmenopausal women with breast cancer. Here the authors examined BMD loss during and after extended adjuvant endocrine therapy, following a 2‐3 year treatment with tamoxifen, subsequent aromatase inhibitor treatment was associated with BMD decrease, but the decline was modest and partially reversible after treatment cessation. The authors concluded that extended endocrine therapy was not associated with a higher incidence of osteoporosis.
The DATA study (NCT00301457) compared 6 and 3 years of anastrozole in postmenopausal women with hormone receptor‐positive early breast cancer after 2–3 years of tamoxifen. Patients with ...chemotherapy‐induced ovarian function failure (CIOFF) were also eligible, but could be at risk of ovarian function recovery (OFR). The current analysis compared the survival of women with CIOFF with definitely postmenopausal women and examined the influence of OFR on survival. Therefore, we selected patients from the DATA study aged 45–57 years at randomization who had received (neo)adjuvant chemotherapy. They were classified by reversibility of postmenopausal status: possibly reversible in case of CIOFF (n = 395) versus definitely postmenopausal (n = 261). The former were monitored by E2 measurements for OFR. The occurrence of OFR was incorporated as a time‐dependent covariate in a Cox‐regression model for calculating the hazard ratio (HR). We used the landmark method to calculate residual 5‐year survival rates. When comparing CIOFF women with definitely postmenopausal women, the survival was not different. Among CIOFF women with available E2 follow‐up values (n = 329), experiencing OFR (n = 39) had an unfavorable impact on distant recurrence‐free survival (HR 2.27 95% confidence interval CI 0.98–5.25; p = 0.05 and overall survival (HR 2.61 95% CI 1.11–6.13; p = 0.03). After adjusting for tumor features, the HRs became 2.11 (95% CI 0.89–5.02; p = 0.09) and 2.24 (95% CI 0.92–5.45; p = 0.07), respectively. The residual 5‐year rate for distant recurrence‐free survival was 76.9% for women with OFR and 92.1% for women without OFR, and for 5‐year overall survival 80.8% and 94.4%, respectively. Women with CIOFF receiving anastrozole may be at increased risk of disease recurrence if experiencing OFR.
What's new?
In postmenopausal women with hormone receptor‐positive breast cancer, aromatase inhibitors (AIs) can prevent disease recurrence and improve survival better than tamoxifen. However, AI‐monotherapy should not be used in premenopausal women, as it can stimulate the estradiol production. Here, the authors investigated the effect of the AI anastrozole after prior tamoxifen in women with chemotherapy‐induced ovarian function failure (CIOFF) versus postmenopausal women. The Survival was comparable for definitely postmenopausal women and those with CIOFF. However, women with CIOFF whose ovarian function returned had a poorer survival, despite regular monitoring of the estradiol levels.
Purpose
Neoadjuvant systemic treatment (NST) is increasingly administered in breast cancer patients. This study was conducted to identify predictors for tumor response in the breast and axilla.
...Methods
All female patients with nonmetastatic, noninflammatory breast cancer receiving NST between 2003‐2013 at the Catharina Cancer Institute in Eindhoven, The Netherlands, were included.
Results
The majority of 216 of the 337 patients receiving NST (65%) presented with a cT2 tumor. In 159 patients (47%), the axilla was clinically node positive. A pathologic complete response (pCR) in the breast was achieved in 83 patients (24.6%), and a pCR in the axilla in 65 node‐positive patients (40.9%). The triple‐negative (OR 4.29, 95% CI 2.15‐8.55) and hormone receptor (HR)‐negative/HER2‐positive tumors (OR 3.73, 95% CI 1.59‐8.75) were associated with in‐breast pCR. Patients with invasive lobular carcinoma (ILC) were less likely to experience in‐breast pCR (OR 0.10, 95% CI 0.01‐0.73) than those with invasive ductal cancer. Axillary pCR was found in 65 clinically node‐positive patients (41%). Axillary pCR was more likely to occur in HR‐positive/HER2‐positive (OR 6.24, 95% CI 1.86‐20.90) and HR‐negative/HER2‐positive tumors (OR 6.41, 95% CI 1.95‐21.06), compared to HER2‐negative disease. In‐breast pCR was strongly associated with axillary pCR (OR 10.89, 95% CI 4.20‐28.22).
Conclusion
Response to NST in the breast and axilla is largely determined by receptor status, with high pCR rates occurring in HER2‐positive and triple‐negative tumors. For axillary pCR, in‐breast pCR and HER2‐positive disease are the most important predictive factors.
Neoadjuvant chemoradiation might increase anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. The aim of this study was to ...determine the influence of radiation dose on the incidence of leakage and stenosis.
Fifty-three patients with esophageal cancer received neoadjuvant chemoradiation (23 × 1.8 Gy) (combined with Paclitaxel and Carboplatin) followed by a transhiatal esophagectomy between 2009 and 2011. On planning CT, the future anastomotic region was determined and the mean radiation dose, V20, V25, V30, V35 and V40 were calculated. Logistic regression analysis was conducted to examine determinants of anastomotic leakage and stenosis.
Anastomotic leaks occurred in 13 of 53 patients (25.5%) and anastomotic stenosis occurred in 24 of 53 patients (45.3%). Median follow-up was 20 months. Logistic regression analysis showed that mean dose, V20-V40, age, co-morbidity, method of anastomosis, operating time and interval between last radiotherapy treatment and surgery were not predictors of anastomotic leakage and stenosis.
A radiation dose of 23 × 1.8 Gy on the future anastomotic region has no influence on the occurrence of anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by transhiatal esophagectomy.
Recurrences in the internal mammary lymph nodes (IMLN) are very rare, despite the fact that these nodes remain untreated in most patients. The aim of this study was to assess the chance for IMLN ...recurrence in a large patient series and to get insight into diagnostics, treatment and prognosis of this type of recurrence. Follow-up of nearly 6000 breast cancer patients resulted in the tracing of only six patients with IMLN recurrence. IMLN recurrence was defined as breast cancer recurrence in an internal mammary lymph node without a distant metastasis before the recurrence and confirmed by cytology and/or CT-scan. The time interval between diagnosis of the primary tumor and the recurrence varied between 5 months and 8 years and 6 months. One patient showed no symptoms, the other five all had a swelling and one of them also had pain. The size of the parasternal swelling varied from 30 to 90 mm; in one patient the size was unknown. Treatment resulted in a complete remission in four patients. In five of the six patients distant metastases occurred. The time interval between IMLN recurrence and the diagnosis of distant metastasis varied between 0 and 37 months. One patient was still free of distant metastasis in the time of this study. This large population-based study confirms the almost negligible risk of clinically apparent IMLN recurrence. Considering the high percentage of positive lymph nodes in studies evaluating sentinel node biopsy of the internal mammary chain, it becomes clear that just a fraction of these becomes clinically apparent as a recurrence. In almost all patients with IMLN it is a forerunner of metastatic disease.
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