Ductal Carcinoma in Situ: A French National Survey. Analysis of 2125 Patients.

BACKGROUND: Ductal carcinoma in situ (DCIS) represents 15% of all breast cancers in France. The first national survey was conducted in 2003. The present multi-center real-life practice survey aimed at assessing possible changes in demographic, clinical, pathologic, and treatment features. MATERIAL AND METHODS: From March 2014 to September 2015, patients diagnosed with DCIS from 71 centers with complete information about age, diagnostic features, and treatment modalities were prospectively included. RESULTS: A total of 2125 patients with a median age of 58.6 years from 71 centers were studied. DCIS was diagnosed by mammography in 87.5% of cases. Preoperative biopsy was performed in 96% of cases. The median tumor size was 15 mm. Nuclear grade was low, intermediate, and high in 12%, 36%, and 47% of cases, respectively. Margins were considered to be negative in 83% of cases. Overall mastectomy and lumpectomy rates were 25% and 75%, respectively. The immediate breast reconstruction rate was 50%. Sentinel node biopsy and axillary dissection rates were 41% and 2.6%, respectively. After lumpectomy, 97% of patients underwent radiotherapy, and 32% received a boost dose. Only 1% of patients received endocrine therapy. Compared with our previous survey, the median tumor size remained the same, and the proportion of high-grade lesions increased by 9%. The mastectomy rate decreased by 4%. CONCLUSIONS: The clinical practice identified in this survey complies with French DCIS guidelines. About 10% of patients with low-grade DCIS may be eligible to participate in treatment de-escalation trials.

Outcome and prognostic factors in breast sarcoma: a multicenter study from the rare cancer network.

BACKGROUND AND PURPOSE: Breast sarcoma (BS) is a rare tumour. While surgical resection is the primary treatment, the role of radiation therapy (RT) and chemotherapy remains unclear. This study aimed at defining prognostic factors and treatment strategies. MATERIALS AND METHODS: Data from 103 patients treated between 1976 and 2002 were collected. The median age was 55 years (range: 13-86); the median histological tumour size was 4.45 cm (range: 0.8-22). There were 42 angiosarcomas. Surgery consisted of wide excision in 34 cases, and total mastectomy in 69 cases. A total dose of 50 Gy in 25 fractions was delivered in 50 patients. At the completion of treatment, 89 patients had no residual tumour. RESULTS: After a median follow-up of 64 months, 56 patients developed recurrent disease: 38 presented a local relapse and 37 developed distant metastases. The 5-year disease-free survival (DFS) and overall survival (OS) were 44% (95% confidence interval [CI], 39-49%) and 55% (95% CI, 50-60%), respectively. In multivariate analysis, favourable prognostic factors for better local control were: no residual tumour after treatment, no cellular pleomorphism, and histology other than angiosarcoma. For DFS, the five favourable prognostic factors were non-menopausal status, no residual tumour after treatment, non-angiosarcoma histology, absence of tumour necrosis, and grade 1-2 histology. CONCLUSION: While angiosarcoma has the worst prognosis, the outcome of the other types of sarcomas may be worsened by residual tumour after loco-regional treatment and high grade histology, a classical prognostic factor of the other soft tissue sarcomas. During surgical procedure axillary dissection is not mandatory.

Breast-conserving surgery and radiotherapy: a possible treatment for lobular carcinoma in situ?

Lobular carcinoma in situ (LCIS) is generally treated by conservative surgery alone and less often by mastectomy. We report our experience using conservative surgery and whole breast irradiation (WBI) for the treatment of patients with LCIS. From 1980 to 1992, 25 women with a median age of 54 years underwent lumpectomy (20) or quadrantectomy (5) and WBI (median dose: 52 Gy) for treatment of their LCIS. Five cases had palpable lesions, 19 were found by mammography alone and one case was found due to nipple discharge. Twelve women received tamoxifen at 20 mg/day for 2 years. With a median follow-up of 153 months (range 58-240), only one local recurrence was observed. The global rate of bilateral carcinoma was 17.6% (two synchronous and one metachronous). Until now, no case of LCIS treated by lumpectomy and radiation therapy has been reported in detail in the literature. After biopsy alone for LCIS, a subsequent infiltrating carcinoma occurs in approximately 15% of cases. Thus, classical radiosurgical therapy should represent an interesting alternative both for limited surgery alone and mastectomy, both of which have been proposed as sole treatments for LCIS.

Lobular carcinoma in situ (LCIS) of the breast: is long-term outcome similar to ductal carcinoma in situ (DCIS)? Analysis of 200 cases.

BACKGROUND: Lobular carcinomas in situ (LCIS) represent 1-2% of all breast cancers. Both significance and treatment remain widely debated, as well as the possible similarities with DCIS. MATERIALS AND METHODS: Two hundred patients with pure LCIS were retrospectively analyzed in seven centres from 1990 to 2008. Median age was 52 years; 176 patients underwent breast-conserving surgery (BCS) and 24 mastectomy. Seventeen patients received whole breast irradiation (WBRT) after BCS and 20 hormonal treatment (15 by tamoxifen). RESULTS: With a 144-month median follow-up (FU), there were no local recurrences (LR) among 24 patients treated by mastectomy. With the same FU, 3 late LR out of 17 (17%) occurred in patients treated by BCS and WBRT (with no LR at 10 years). Among 159 patients treated by BCS alone, 20 developed LR (13%), but with only a 72-month FU (17.5% at 10 years). No specific LR risk factors were identified. Three patients developed metastases, two after invasive LR; 22 patients (11%) developed contralateral BC (59% invasive) and another five had second cancer. CONCLUSIONS: LCIS is not always an indolent disease. The long-term outcome is quite similar to most ductal carcinomas in situ (DCIS). The main problems are the accuracy of pathological definition and a clear identification of more aggressive subtypes, in order to avoid further invasive LR. BCS + WBRT should be discussed in some selected cases, and the long-term results seem comparable to DCIS.

Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience.

PURPOSE: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. METHODS AND MATERIALS: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. RESULTS: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p <0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged < or =40, 41-60, and > or =61 years (p <0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p <0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p <0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively. CONCLUSION: Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women <40 years and/or in the case of incomplete excision.

Natural history of node-negative breast cancer: are conventional prognostic factors predictors of time to relapse?

The purpose of this study was to determine a subpopulation of node-negative breast cancer patients at high risk of metastases and to analyse the relationship between conventional prognostic factors and the onset of metastatic disease. Patients with node-negative breast cancer, who were not receiving systemic adjuvant therapy, were prospectively enrolled into a multicentre study. We studied the onset of metastatic disease in relation to family history, age, and tumour characteristics of 2683 registered patients, 2213 were available for analysis. Median follow-up was 100 months. Metastatic disease-free survival was 88% at 5 years and 80% at 10 years. The two strongest prognostic factors in a multivariate analysis tumour Scraff, Bloom and Richardson (SBR) grade (P<0.0001) and size (P<0.02), were used to classify patients into three groups with different risks of relapse at 10 years: (1) lowest (8.4%) risk: SBR I and < or =1 cm; (2) intermediate (20%) risk: SBR I and >1 cm or SBR II or SBR III and < or =2 cm; (3) highest (32%) risk: SBR II or SBR III and >2 cm. A peak in the incidence of metastases was noted between 2 and 4 years, and a nadir between 6 and 8 years, after surgery. SBR grade is a highly predictive factor in node-negative breast cancer. The time course of the appearance of metastases is not linear. Prognostic factors are related to the height of an early peak in the occurrence of metastases rather than to the timing of this peak.

Breast conserving treatment (BCT) for stage I-II breast cancer in elderly women: analysis of 927 cases.

INTRODUCTION: Few breast conserving treatment (BCT) data include women older than 70. MATERIAL: 910 women older than 70 were treated by BCT for stage I-II BC, with 670 pT(1) (72.3%), 245 pT(2) (26.4%) and 12 pT(x) (1.3%). Axillary nodal involvement occurred in 30.7% of cases. ER and PgR were positive in 85% and 71% of cases. Radiotherapy (RT) was delivered in all patients, tamoxifen in 55.8% and chemotherapy in 4.8%. RESULTS: With a 65-month median follow-up, 28 (3%) local recurrences (LR) and 83 (9.1%) metastases occurred. Second cancer occurred in 51 (5.6%) patients. The 8-year overall survival (OS) and disease-specific survival (DSS) rates were 74% and 90%. The 8-year OS and DSS rates were 77% and 92% versus 65% and 84% in pT(1) versus pT(2) patients (p=0.01). 676 patients were in complete remission (74.3%); 22 were evolutive (2.4%). 206 patients died (22.6%). CONCLUSION: Our study confirms the excellent local control in elderly patients treated by BCT with RT and identifies subgroups at high risk of distant relapse that should be treated more aggressively.

Joint pain with aromatase inhibitors: abnormal frequency of Sjögren's syndrome.

OBJECTIVE: Since the results of the ATAC study, women who have undergone surgery for breast cancer and who require adjuvant hormone therapy are often treated with aromatase inhibitors. With these treatments, joint pain is frequent (30% to 40%) and quite often disabling (5% to 10%). Our objective was to investigate the origin of the pain induced by the anti-aromatases. METHODS: Twenty-four women of mean age 59 years with joint pain of > 5/10 on a visual analog scale underwent a rheumatological consultation and systematic laboratory tests. RESULTS: In 5 patients, pain was considered to have a well defined cause: osteoarthritis, shoulder tendinitis, or paraneoplastic aponeurositis. The other 19 patients had inflammatory pain of the fingers, wrists, shoulders, forefeet, ankles, or knees, with slight synovial thickening of the PIP and MCP joints. Two had an inflammatory syndrome on laboratory tests. Nine of these patients had antinuclear antibodies (ANA > 1/160 on HEp-2 cells) and 4 had rheumatoid factors (> 20 U). Ten patients had sicca syndrome of the eyes or mouth, 7 had probable Sjögren's syndrome according to the San Diego criteria, and one had definite Sjögren's syndrome. One had rheumatoid arthritis, one had Hashimoto thyroiditis, and 2 had positive hepatitis C serology. CONCLUSION: Is the almost total estrogen depletion induced by aromatase inhibitors conducive to the development of sicca syndromes with ANA? Our results should be considered in relation to the Sjögren-like syndromes occurring in aromatase knock-out mice as recently reported.

[Influence of the delay between conservative surgery and radiation therapy on local relapse in node-positive breast tumor]. / Rôle du délai chirurgie conservatrice-radiothérapie sur les rechutes locales du cancer du sein avec envahissement ganglionnaire.

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p < 0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.

Influence of the time between surgery and radiotherapy on local recurrence in patients with lymph node-positive, early-stage, invasive breast carcinoma undergoing breast-conserving surgery: results of the French Adjuvant Study Group.

BACKGROUND: Radiotherapy (RT) after breast-conserving surgery (BCS) has produced significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was shown previously that a delay in the initiation of RT resulted in a higher local recurrence (LR) rate. In the current retrospective analysis, the authors investigated whether the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after BCS in patients with early-stage, lymph node-positive BC. METHODS: Among 7 French Adjuvant Study Group trials, 1831 patients were assessable, including 475 patients who received RT directly after BCS (95 patients received no adjuvant therapy, and 380 patients received hormone therapy), 567 patients who received RT after the third chemotherapy (CT) cycle (250 patients received 1-3 courses, and 317 patients received 4-6 courses), and 789 patients received RT after the sixth CT cycle. In the 1356 patients who received CT, the regimens consisted of fluorouracil 500 mg/m(2); epirubicin 50 mg/m(2), 75 mg/m(2), or 100 mg/m(2); and cyclophosphamide 500 mg/m(2) in 83.5% of patients. RESULTS: After a median follow-up of 102 months, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (P < 0.0001). It was worse in patients who received 1-3 CT cycles (P = 0.02). Patients who received hormone therapy were less likely to develop LR (P = 0.02). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size > 2 cm and no hormone therapy were prognostic factors. CONCLUSIONS: In the study population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormone therapy. The number of CT courses could modified this risk.