[Ductal carcinoma in situ diagnosis: 3 French national guidelines]. / Diagnostic du carcinome canalaire in situ : 3 recommandations nationales françaises.

OBJECTIVE: Since the last guidelines published by the French National Cancer Institute (INCa) and the learning society "Société française de sénologie et de pathologie mammaire (SFSPM)" in 2009 about diagnosis and management of ductal carcinoma in situ, new data raised issues about overdiagnosis and its consequences, overtreatment. Therefore, an update was necessary, to provide healthcare professionals up-to-date guidelines and study therapeutic desescalation in particular. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary experts workgroup. The recommendations are thus based on the best available evidence and experts agreement. Prior to publication, the guidelines are also reviewed by more than 100 independent practitioners in cancer care delivery. RESULTS: This article presents French guidelines about MRI and vacuum assisted breast biopsy indications for DCIS diagnosis and the management of low-grade DCIS.

Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA).

As the mean age of the global population increases, breast cancer in older individuals will be increasingly encountered in clinical practice. Management decisions should not be based on age alone. Establishing recommendations for management of older individuals with breast cancer is challenging because of very limited level 1 evidence in this heterogeneous population. In 2007, the International Society of Geriatric Oncology (SIOG) created a task force to provide evidence-based recommendations for the management of breast cancer in elderly individuals. In 2010, a multidisciplinary SIOG and European Society of Breast Cancer Specialists (EUSOMA) task force gathered to expand and update the 2007 recommendations. The recommendations were expanded to include geriatric assessment, competing causes of mortality, ductal carcinoma in situ, drug safety and compliance, patient preferences, barriers to treatment, and male breast cancer. Recommendations were updated for screening, primary endocrine therapy, surgery, radiotherapy, neoadjuvant and adjuvant systemic therapy, and metastatic breast cancer.

Monitoring Breast Cancer Care Quality at National and Local Level Using the French National Cancer Cohort.

PURPOSE: The French National Cancer Institute has developed, in partnership with the French National Authority for Health, breast cancer-specific Care Quality, and Safety Indicators (BC QIs). With regard to the most common form of cancer, our aim is to support local and national quality initiatives, to improve BC pathways and outcomes, reduce heterogeneity of practice and regional inequities. In this study, we measure the BC QIs available in the French National medico-administrative cancer database, the French Cancer Cohort, for 2018. MATERIALS AND METHODS: BC QIs are developed according to the RAND method. QIs are based on good clinical practice and care pathway recommendations. QI computation should be automatable without any additional workload for data collection. They will be published annually for all stakeholders, and especially hospitals. RESULTS: Finally, ten feasible and pertinent QIs were selected. In France, BC care was found to be close to compliance with most QIs: proportion of patients undergoing biopsy prior to first treatment (94.5%), proportion of patients undergoing adjuvant radiotherapy after breast-conserving surgery for BC (94.5%), proportion of women undergoing radiotherapy within 12 weeks after surgery and without chemotherapy (86.2%), proportion of DCIS patients undergoing immediate breast reconstruction (54.3%) and proportion of women with NMIBC undergoing breast reintervention (14.4%). However, some are still far from their recommended rate. In particular, some QIs vary considerably from one region, or one patient, to another. CONCLUSION: Each result needs to be analyzed locally to find care quality leverage. This will strengthen transparency actions aimed at the public.

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.

The 2018 assisi think tank meeting on breast cancer: International expert panel white paper.

We report on the second Assisi Think Tank Meeting (ATTM) on breast cancer which was held under the auspices of the European Society for RadioTherapy & Oncology (ESTRO). In discussing in-depth current evidence and practice it was designed to identify grey areas in diverse forms of the disease. It aimed at addressing uncertainties and proposing future trials to improve patient care. Before the meeting, three key topics were selected: 1) primary systemic therapy, mastectomy, breast reconstruction and post-mastectomy radiation therapy, 2) therapeutic options in ductal carcinoma in situ, and 3) therapy de-escalation in early stage breast cancer. Clinical practice in these areas was investigated by means of an online questionnaire. The time lapse period between the survey and the meeting was used to review the literature and on-going clinical trials. At the ATTM both were discussed in depth and research protocols were proposed.

The effect of adjuvant radiotherapy on mortality differs according to primary tumor location in women with node-positive breast cancer.

PURPOSE: To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC). PATIENTS AND METHODS: Data were abstracted from the SEER database for 24,410 women aged 25-95 years, diagnosed between 1988-1997 with nonmetastatic T1-T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups were evaluated with Wald test. RESULTS: Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional reduction of mortality in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with mastectomy. In this subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality. CONCLUSION: Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy may be offset by excess toxicities in the latter subgroup.

[Ductal carcinoma in situ in 2019: Diagnosis, treatment, prognosis]. / Les carcinomes canalaires in situ en 2019 : diagnostic, traitement, pronostic.

Ductal carcinoma in situ (DCIS) currently represents up to 15% of the newly diagnosed breast cancers, and are almost always detected by microcalcifications. Global prognosis is good (3% of 15-year specific mortality) but invasive local recurrences (LR) can lead to metastasis in 12-15% of the cases. Breast conserving surgery with whole breast irradiation is the main treatment (reducing LR by 50%), but mastectomy (with or without reconstruction) is performed in about 30% of the cases due to wide lesion size and/or multicentricity. The role of tamoxifen remains unclear. Axillary dissection is needless but sentinel node biopsy is proposed in case of micro-invasion suspicion (large lesions with high grade). The main factors of LR are young age (≤40 years) incomplete excision, and high nuclear grade with comedonecrosis. Several studies on "therapeutic descalation" are still ongoing in order to identify the "low risk" DCIS (about 10% of the cases) in which radiotherapy could be safely omitted.

Should Adjuvant Radiation Therapy Be Systematically Proposed for Male Breast Cancer? A Systematic Review.

BACKGROUND: Guidelines for radiotherapy in male breast cancer (MBC) are lacking. Some extrapolate the results from female breast cancer trials, while others advocate systematic adjuvant irradiation. We evaluated clinical practices and outcomes with respect to radiation therapy in MBC treated with locoregional irradiation in the adjuvant setting using a systematic literature review. MATERIAL AND METHODS: We included studies with data about adjuvant radiotherapy published between 1984 and 2017 and including at least 40 patients. RESULTS: We found 29 retrospective series, 10,065 men were diagnosed with breast cancer; 3-100% (mean=54%) received adjuvant radiotherapy. Tumor size and nodal involvement were the strongest prognostic factors. Approximatively half of all cases had nodal metastases. Radiation therapy improved locoregional control in six series, overall survival in three and distant metastasis-free survival in one. CONCLUSION: MBC is diagnosed at a highly advanced stage and may be linked with poorer outcomes. Adjuvant radiation therapy must, at least, be proposed to men with positive nodes. Despite the large number of cases gathered here, arguments for radiotherapy in other prognostic subgroups (especially in pN0) may exist but are not well supported.

Quality indicators in breast cancer care: An update from the EUSOMA working group.

In 2010, EUSOMA published a position paper, describing a set of benchmark quality indicators (QIs) that could be adopted by breast centres to allow standardised auditing and quality assurance and to establish an agreed minimum standard of care. Towards the end of 2014, EUSOMA decided to update the paper on QIs to consider and incorporate new scientific knowledge in the field. Several new QIs have been included to address the need for improved follow-up care of patients following primary treatments. With regard to the management of elderly patients, considering the complexity, the expert group decided that, for some specific quality indicators, if centres fail to meet the minimum standard, older patients will be excluded from analysis, provided that reasons for non-adherence to the QI are specified in the clinical chart and are identified at the review of the clinical records. In this way, high standards are promoted, but centres are able to identify and account for the effect of non-standard treatment in the elderly. In the paper, there is no QI for outcome measurements, such as relapse rate or overall survival. However, it is hoped that this will be developed in time as the databases mature and user experience increases. All breast centres are required to record outcome data as accurately and comprehensively as possible to allow this to occur. In the paper, different initiatives undertaken at international and national level to audit quality of care through a set of QIs have been mentioned.

The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS)?

Lobular carcinoma in situ was first described over 60 years ago. Despite the long history, it continues to pose significant difficulties in screening, diagnosis, management and treatment. This is partly due its multi-focal and bilateral presentation, an incomplete understanding of its biology and natural history and perpetuation of misconceptions gathered over the last decades. In this review, the working group on behalf of EUSOMA has attempted to summarise the current thinking and management of this interesting lesion.

[Not Available]. / Cancer du sein au stade précoce : stopper la désescalade en radiothérapie.

REFLEXIONS ABOUT NEW STRATEGIES OF RADIOTHERAPY FOR EARLY BREAST CANCER: Radiotherapy (RT) remains a major treatment element in early breast cancer, with a major impact on local control and survival. For ductal carcinoma in situ (DCIS), RT reduces local recurrence (LR) rates by 50 to 60 % after conservative surgery (both in situ and invasive). This was confirmed by four randomized trials and one meta-analysis. For infiltrating breast cancers (IBC), RT also reduces LR rates by 65 to 75 % after conservative surgery. Boost allows an additional reduction of LR. RT is efficient in all age categories, but hypofractionated schemes are particularly adapted to elderly women. Partial breast irrradiation techniques are very much heterogeneous and lack follow-up. They should be used in LR low-risk patients only and in the frame of controlled studies. Locoregional RT for high-risk patients (especially in pN+) remains essential to reduce the locoregional recurrence rate and to increase survival, as confirmed in several meta-analyses. Four studies showed a survival benefit (2-3 %), thanks to internal mammary chain irradiation in LR high-risk patients. Moreover, axillary RT seems to be a likely valuable alternative to axillary dissection in case of sentinel node invasion. Finally, with the modern techniques and dosimetric optimization, RT toxicity was reduced, or even cancelled, arousing hope for a better increased benefit for the patients in the future.

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.

Hypofractionated irradiation in elderly patients with breast cancer after breast conserving surgery and mastectomy : Analysis of 205 cases.

BACKGROUND: Several randomized trials and meta-analyses confirmed a wide benefit of radiotherapy (RT), both after breast conserving surgery (BCS) and mastectomy. However, many elderly women don't receive RT. Hypofractionated (HF) RT allows « simplified ¼ and more accessible treatments with equivalent results to classic RT in three large randomized trials. However, there are few available data on HF-RT for nodal irradiation, as well as for the boost. METHODS: We evaluated patients treated for IBC by HF-RT between 2004 and 2012 in two regional cancer centres. We used an original scheme delivering 45 Gy in 15 fractions three times a week, both after BCS or mastectomy, with or without nodal irradiation. After BCS, a 9 Gy boost in 3 fractions was delivered. Local, regional and distant recurrences were assessed, as well as acute and late cutaneous, cardiac or pulmonary toxicities. RESULTS: 205 patients were analysed, 116 after BCS (57 %) and 89 after mastectomy (43 %). Median age was 81 years (range: 52-91); 44 % had axillary nodal involvement (pN+). The Nottingham Prognostic Index (NPI) scored 0, 1, 2 and 3 in 10 %, 27 %, 44 % and 19 % of the cases. A nodal HF-RT was delivered in 65 patients (32 %) and boost in 98 patients (84 % of BCS) by 9 Gy/3 fr scheme. Fifty (24 %) patients underwent chemotherapy and 156 (75 %) hormonal treatment. With a 49-month median follow-up, 3/116 (2.6 %) patients and 4/89 (4.5 %) had local recurrence (LR) after BCS and mastectomy, respectively. The overall 5-year LR rate was 4.4 %. In univariate and multivariate analysis, LR risk factors were: high NPI (HR 5.46; p = 0.028), and triple negative tumour (HR 9.78; p = 0.006). Only 8 (4.5 %) patients had grade III skin toxicity; 29 (14 %) late fibrosis and 16 (8 %) telangiectasia. No pulmonary or cardiac toxicity was observed. CONCLUSION: Our HF-RT scheme (with or without nodal irradiation) confirms in elderly patients the data from randomized trials, both after BCS or mastectomy. Toxicity seems very acceptable but requires a longer follow-up. A larger evaluation is still ongoing in several other centres in France.

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 stage I-II breast cancer in elderly women.

PURPOSE: To assess breast-conserving therapy results in elderly patients with early-stage breast cancer (clinical Stage I-II). METHODS AND MATERIALS: Between 1979 and 1998, 196 women (200 treated breasts) aged > or =70 years (median age, 72.5 years) were treated with breast-conserving therapy (lumpectomy or quadrantectomy with axillary lymph node dissection and radiotherapy). Pathologic axillary node involvement was found in 51 patients (28%). Two-thirds of patients received tamoxifen, and 16% received chemotherapy. RESULTS: At a median follow-up of 59 months, 3 patients (1.5%) had developed local recurrence and 20 (10.2%) distant metastases. The overall survival rate was 81% and 62% at 5 and 10 years, respectively. The corresponding disease-specific survival rates were 92% and 88%. Axillary nodal involvement was the only statistically significant risk factor for the development of metastases (p = 0.0035). Arm mobility impairment and arm lymphedema each occurred in 5 patients. In another 5 patients, a thromboembolic event occurred during tamoxifen treatment. CONCLUSION: Elderly women tolerate breast-conserving therapy, including radiotherapy, well and have excellent rates of locoregional control and disease-specific survival.

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.

Adjuvant radiotherapy for breast cancer: effects of longer follow-up.

BACKGROUND AND PURPOSE: Recent and large trials of adjuvant radiotherapy for breast cancer have shown an overall survival benefit in favour of radiotherapy. However, with longer follow-up the late lethal toxicity of radiotherapy might reduce the overall survival benefits. In this paper we investigate more deeply this hypothesis. PATIENTS AND METHODS: Overviews of the Early Breast Cancer Trialists' Collaborative Group provide uniform data on more than 50 unconfounded trials on adjuvant radiotherapy for early breast cancer. These data were published at regular intervals: 1987, 1990, 1995, and 2000. The odds ratios (death of any cause) were borrowed to compare the benefits of adjuvant radiotherapy between the early publications and the more mature data of the same trials. Statistical significance is calculated following logrank statistics. The comparison of odds ratios (radiotherapy versus surgery only) was done for the whole group of trials, for the older (patients accrual started in 1970 or earlier) and the more recent trials (patient accrual started after 1970), and for the large (>or=600 patients) and the small trials (<600 patients). RESULTS: Comparison of early with more mature data reveals that the odds ratios for overall survival remain stable as data become more mature. The analyses of trials' age and trials' size, as predictors of overall survival benefit, indicate that these factors become statistically more significant with increasing maturity of the trials. In the large recent trials an overall survival benefit due to radiotherapy (odds reduction) of 10, 10, 12 and 13%, respectively P<0.3, 0.2, 0.005 and 0.00005 is found in the successive publications. The difference in survival benefit of radiotherapy between the group of large recent trials and group of old or small trials becomes more significant at the successive updates: 10 via 9% and 12 to 13% (odds reductions), with respectively P=0.2, 0.2, 0.004 and 0.00005. CONCLUSIONS: These results support the hypothesis that the survival benefit in the recent trials is an inherent characteristic of the recent and large trials, not influenced by follow-up duration. The effect of radiotherapy as performed in the large recent trials is clinically and statistically significantly different from the effect of radiotherapy in the old or small trials. As a consequence, predictions based on pooled data including old radiotherapy trials should not be extrapolated to modern radiotherapy.

Is radiotherapy needed after adequate local excision of localized DCIS?

Despite the fact that mastectomy remains the safest treatment for ductal carcinoma in situ, breast conserving surgery is still a frequent option. Three randomized trials (NSABP B17- EORTC 10853- UK DCIS) have confirmed a statistically significant reduction of LR rate by the addition of a whole breast irradiation at 50 Gy (RT). The rate of LR, both in situ and invasive, has been reduced by 45-55% with RT, e.g. in the NSABP B-17 trial, with a 129-month follow-up, the overall LR rate decreased from 31.7% to 15.7% (p = 0.001). The RT benefit was confirmed in all subgroups of patients, even with a lack of advantage on survival. Two large retrospective studies (in France and California) also confirmed the benefit of RT after lumpectomy, but with small differences in the subgroup with large excision (and margin width > or = 10 mm). On the other hand, invasive LR can give a 15-20% subsequent metastasis rate. Today, the current whole breast RT using megavoltage photons and provisional CT-scan-based dose distribution is resulting in less than 1% of complications. Until now, no studies have clearly identified patients with a sufficiently low LR risk to justify the lack of RT after lumpectomy. Finally, DCIS treatment requires a close multidisciplinary collaboration; moreover surgery and radiotherapy should be used jointly to obtain optimal long-term local control, such as for so many tumors.