Radiotherapy of breast cancer.

Adjuvant radiotherapy is an essential component of the treatment of breast cancer. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. A boost dose over the tumour bed is required if the patient is younger than 50 years-old. Partial breast irradiation could be routinely proposed as an alternative to whole breast irradiation, but only in selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neoadjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra- and infraclavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Hypofractionation regimens (42.5Gy in 16 fractions, or 41,6Gy en 13 or 40Gy en 15) are equivalent to conventional irradiation and must prescribe after tumorectomy in selected patients. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with or after radiotherapy.

The Assisi Think Tank Meeting Survey of post-mastectomy radiation therapy in ductal carcinoma in situ: Suggestions for routine practice.

BACKGROUND: Risk factors for local recurrence after mastectomy in ductal carcinoma in situ (DCIS) emerged as a grey area during the second "Assisi Think Tank Meeting" (ATTM) on Breast Cancer. AIM: To review practice patterns of post-mastectomy radiation therapy (PMRT) in DCIS, identify risk factors for recurrence and select suitable candidates for PMRT. METHODS: A questionnaire concerning DCIS management, focusing on PMRT, was distributed online via SurveyMonkey. RESULTS: 142 responses were received from 15 countries. The majority worked in academic institutions, had 5-20 years work-experience and irradiated <5 DCIS patients/year. PMRT was more given if: surgical margins <1 mm, high-grade, multicentricity, young age, tumour size >5 cm, skin- or nipple- sparing mastectomy. Moderate hypofractionation was the most common schedule, except after immediate breast reconstruction (57% conventional fractionation). CONCLUSIONS: The present survey highlighted risk factors for PMRT administration, which should be further evaluated.

EUSOMA position regarding breast implant associated anaplastic large cell lymphoma (BIA-ALCL) and the use of textured implants.

During the last two decades the number of breast implants used in aesthetic, oncologic and risk reducing surgery has increased substantially mainly due to the improvement and confirmed safety of these devices. Since identification of the first case of anaplastic large cell lymphoma associated with a breast implant (BIA-ALCL) 20 years ago, there has been an increase in the number of reports of this very rare disease, demonstrating a clear association with breast implants. Whilst the majority of cases are localised and cured by implant removal and full capsulectomy, a small percentage require chemotherapy and the mortality rate is very low. The evidence linking BIA-ALCL to implant surface texturing, as the majority of cases were diagnosed in patients with textured implants, has raised concerns about the long term safety of these devices resulting in patient and regulatory authority concerns globally. We hereby present the current published knowledge about the link between BIA-ALCL and implant surface texture and a review of current regulatory and professional body advice across Europe, which may enable a better understanding of this rare disease, how to manage and ultimately prevent it. We conclude by giving EUSOMA recommendation, towards the unnecessary change in attitudes towards implant based surgery, according to the most recent available published evidence as long as patients are properly informed about the risk of BIA-ALCL.

[Hypofractionated whole breast irradiation (WBRT): Results and indications]. / Irradiation hypofractionnée du sein : résultats et indications.

Breast irradiation after breast-conserving surgery is essential for maximizing local control and overall survival. The increase of breast cancer (BC) incidence, constraints of classical five weeks (w) radiation regimens and scarcity of radiotherapy units have led to test short hypofractionated WBRT schemes. One pilot study and three prospective randomized trials have tested various hypofractionated regimens of WBRT. About 7000 patients were included and follow-up ranged from 5 to 12 years. The conclusion of these trials is similar, showing local control and toxicity equivalent to these of the standard regimens. Three schemes are now clearly validated: 42.5Gy/16fr/3w, 40Gy/15fr/3w, or 42Gy/13fr/5w. However, the majority of included patients had favorable prognostic factors, were treated to the breast only and the boost dose, when indicated, was delivered with a standard fractionation. Therefore, we recommend the regimens preferentially in patients treated to the breast only, and without nodal involvement. These studies did not evaluate the addition of a boost dose with a hypofractionated scheme. If a boost is to be given, a standard fractionation should be used. Particular care should be taken to avoid heterogeneities leading to high fraction doses to organs at risk (lung and heart).

[Radiotherapy of breast cancer]. / Radiothérapie du cancer du sein.

In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with radiotherapy.

Breast-conserving treatment for ductal carcinoma in situ: Impact of boost and tamoxifen on local recurrences.

PURPOSE: Ductal carcinoma in situ represents 15 to 20% of all breast cancers. Breast-conserving surgery and whole breast irradiation was performed in about 60% of the cases. This study reports local recurrence rates in patients with ductal carcinoma in situ treated by breast-conserving surgery and whole breast irradiation with or without boost and/or tamoxifen and compares different therapeutic options in two European countries. PATIENTS AND METHODS: From 1998 to 2007, 819 patients with pure ductal carcinoma in situ were collected, both in France (266) and Italy (553). Median age was 56. All underwent breast-conserving surgery and whole breast irradiation; 391 (48%) received a boost (55% in France and 45% in Italy, P=0.017) and 173 (22.5%) tamoxifen (4.5% in France and 32% in Italy, P<0.0001). RESULTS: With a 90-month median follow-up, there were 51 local recurrences (6.2%), including 27 invasive (53%). The 5- and 10-year local recurrence rates were 4% and 8.6%. Two patients developed axillary recurrence and 12 (1.5%) metastases (seven after invasive local recurrence); 41 (5%) patients had contralateral breast cancer. In the multivariate analysis, high nuclear grade and lack of tamoxifen are the most powerful predictors of local recurrence, with 2.6 (95% confidence interval [95% CI]: 1.74-3.89, P=0.0012) and 2.85 (95% CI: 1.42-5.72, P=0.04) odds ratio (OR) estimates, respectively. Age, margin status and boost did not influence local recurrence rates. CONCLUSIONS: This study confirms the ductal carcinoma in situ treatment heterogeneity among countries and the unfavourable prognostic role of nuclear grade. Tamoxifen reduces local recurrence rates and might be considered for some subgroups of patients, but further confirmation is required. The boost usefulness still remains unclear.

Impact of screening on clinicopathological features and treatment for invasive breast cancer: results of two national surveys.

PURPOSE: Several studies showed a breast cancer downstaging due to screening. A first national survey was conducted in France in 2001-2002 to evaluate in the current clinical practice the clinicopathological features and treatments of 1049 firstly operated breast cancers. In order to assess the impact of the national screening program implemented in all regions in France in 2004, a new survey was performed in 2007-2008. MATERIAL: The new survey included 1433 firstly operated breast cancers prospectively collected. These new data were compared to the results of the first national survey. RESULTS: According to TN classification, we found in the second survey T0: 27.6%, T1: 48.6%, T2: 21.3%, T3T4: 3.8% and Tx: 0.7%. Infiltrating ductal and lobular carcinomas represented 80% and 13% of tumours. Hormone receptors were positive in 85.3% and Her-2 overexpressed in 12.4% of tumours (83.9% and 20.6% in the first survey); 68.2% and 32% were pN0 and pN1-3. Lumpectomy and mastectomy were performed in 77% and 23% of the cases. Axillary dissection, sentinel node biopsy or both were performed in 42.6%, 41% and 16.4% of the cases, respectively. Radiotherapy, chemotherapy, hormonotherapy and trastuzumab were given to 93%, 51%, 83% and 9.3% of the patients. Compared with the results from the first survey, we found an increase of infraclinical lesions (T0 from 8.4 to 27.6%) and a wide decrease of pN+ rate (from 44% to 32%). The mastectomy rate was constant (23%), as well as radiotherapy use, whereas chemotherapy use decreased from 62.8 to 55.6%. CONCLUSION: A complete national screening coverage clearly provides a favourable modification of breast cancer clinicopathological features. Both locoregional and adjuvant treatments were greatly downscaled.

[Male breast cancer: prognostic factors, diagnosis and treatment: a multi-institutional survey of 95 cases]. / Le cancer du sein chez l'homme: approche épidémiologique, diagnostique, et thérapeutique: étude multicentrique rétrospective à propos de 95 cas.

OBJECTIVES: The optimal treatment for male breast cancer is not known because male breast cancer is a rare disease. It represents as little as 0.6% of all breast cancers and less than 1% of human cancers. The aim was to analyze the clinical, histological and therapeutic characteristics of 95 men cared for breast cancer between 2000 and 2010 in four hospitals, and determine predictors of poor prognosis to improve care of male breast cancer. METHODS: This study is a multi-institutional survey, retrospective, involving four French institutions: Cancer Institute of the West (ICO), Reunion Island South hospital group, the hospital group of Dax, and the Bergonié Institute. All carcinomas in situ or invasive breast occurred in male patients were included. An analysis of clinical, histological and therapeutic features was performed. Statistical analysis of our study focused on the overall survival of patients and specific method of Kaplan-Meier, enabling search for predictors of poor prognosis. RESULTS: The mean age was 65 years. Thirty-seven percent of patients were overweight or obese. It was in 88% of cases of palpable tumor whose average size was 26.29mm. Ninety patients, none had a lesion palpable T0, 44% T1 tumors, 38% T2 tumors, 3% had a T3 tumors, and finally 10% T4 tumors. The histological type was the most common invasive ductal carcinoma (87%). He found a similar proportion of patients with or without lymph node involvement. N+ patients, capsular rupture was observed in 29% of cases. Receptor positivity was found, estrogen in 95% of cases and progesterone in 83% of cases. Additional irradiation was performed in 75% of patients and chemotherapy in 37% of patients. Overall survival was 79.2% at five years and 70.8% at ten years. Age, tumor size and histological capsular rupture are factors that significantly influence the overall survival and specific. CONCLUSION: Male breast cancer is a different pathology of breast cancer in women. The majority of recommendations suggest treating men who are diagnosed with breast cancer, using the guidelines applied to postmenopausal women treatments. There is no study based on male population that has evaluated these treatment modalities in terms of impact on survival. The diagnosis is usually made at later stages, and tumor size is often greater. Histological characteristics also differ. However, the treatment is almost identical.

Local recurrence after ductal carcinoma in situ breast conserving treatment. Analysis of 195 cases.

PURPOSE: Ductal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival. PATIENTS AND METHODS: This study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS+RT), presenting local recurrences, with a 156-month median follow-up. RESULTS: Eighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P=0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P<0.0007). CONCLUSION: Invasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed.

Adjuvant radiotherapy in the management of axillary node negative invasive breast cancer: a qualitative systematic review.

PURPOSE: To actualize and to detail guidelines used in technical radiotherapy and indications for innovative radiation technologies in early axillary node negative breast cancer (BC). METHODS: Dosimetric and treatment planning studies, phase II and III trials, systematic reviews and retrospective studies were all searched (Medline(®) database). Their quality and clinical relevance were also checked against validated checklists. A level of evidence was associated for each result. RESULTS: A total of 75 references were included. Adjuvant BC radiotherapy (50Gy/25 fractions/5 weeks followed by a tumor boost of 16Gy/8 fractions) is still the standard of care. Overall treatment time could be shortened for patients who present with low local relapse risk BC by using either hypofractionated whole breast irradiation; or accelerated partial breast irradiation. BC IMRT is not used in current practice. CONCLUSION: Our group aimed to provide guidelines for technical and clinical applications of innovative BC radiation technologies.

[Radiotherapy for breast cancer: which strategy in 2012?]. / Radiothérapie des cancers du sein en 2012 : quelles stratégies ?

Postoperative radiotherapy remains essential in breast cancer in 2012. After conserving surgery, it reduces local recurrence risks from 50 to 70%, both for ductal carcinoma in situ and invasive cancers. This was confirmed in several randomized trials and three meta-analyses. The boost increases local control in invasive cancers, but its role should be better defined in ductal carcinoma in situ. Among the latter, there is no clearly identified subgroup for which radiotherapy could be avoided. Local recurrence risk factors are now well-identified both for ductal carcinoma in situ and invasive cancers, with an inclusion, for the latter, of new molecular subgroups. After mastectomy, radiotherapy reduces local recurrence rates from 60 to 70%, especially among patients with axillary nodal involvement, with, in parallel, a 7 to 9% increased survival rate. In order to reduce the waiting list and to avoid under treatment, especially in the elderly, several hypofractionated radiotherapy schemes have been developed for several years. Three randomized trials confirmed similar results to classical radiotherapy. For ten years, several techniques of partial breast irradiation have been developed, with various doses and treated volumes. The optimal indications should be defined according to the new international guidelines.

[Radiotherapy of invasive breast cancer: French national guidelines]. / Radiothérapie du cancer du sein infiltrant : recommandations nationales françaises.

The French National Cancer Institute (INCa) and Société française de sénologie et pathologie mammaire (SFSPM), in collaboration with a multidisciplinary experts group, have published the French national clinical practice guidelines on a selection of 11 currently debated questions regarding the management of invasive breast cancer. Those guidelines are based on a comprehensive analysis of the current published evidence dealing with those issues, secondly reviewed by 100 reviewers. Radiotherapy was concerned by five of the 11 questions: indications for the boost after whole gland irradiation; hypofractionated radiotherapy; partial breast irradiation; indications for mammary internal nodes irradiation, and indications of radiotherapy after neo-adjuvant chemotherapy.

[Hypofractionated whole breast irradiation: Pro and cons]. / Irradiation hypofractionnée dans le cancer du sein : pour ou contre ?

The continuous increase of breast cancer (BC) incidence, the logistic constraints of the protracted standard 5-week radiations regimen have led to test short hypofractionated whole breast radiation therapy schemes. Three prospective randomized trials and a pilot trial have been published. Large numbers of patients were included, with follow-up duration ranging from 5 to 12 years. The conclusions of these trials were similar, showing local control and toxicity equivalent to those of the standard regimen, and supporting the use of three schemes: 42.5 Gy/16 fractions/3 weeks, 40 Gy/15 fractions/3 weeks or 41.6 Gy/13 fractions/5 weeks. However, the patients in these trials had favourable prognostic factors, were treated to the breast only and the boost dose, when indicated, was delivered with a standard fractionation. Hypofractionated treatment can only be recommended in patients treated to the breast only, without nodal involvement, with grade<3 tumours and who are not candidate to chemotherapy. If a boost is to be given, a standard fractionation should be used. Particular care should be taken to avoid heterogeneities leading to high fractional doses to organs at risk (lung and heart).

Radiotherapy for invasive breast cancer: guidelines for clinical practice from the French expert review board of Nice/Saint-Paul de Vence.

PURPOSE: While new strategies for the treatment of invasive breast cancer (BC) are emerging, radiotherapy (RT) modalities are still under debate. The French expert review board of Nice-Saint-Paul de Vence was asked firstly to conduct a qualitative evidence-based systematic review and then to establish clinical practice guidelines for the use of post operative RT in invasive BC. METHODS AND MATERIALS: A search to identify eligible studies was undertaken using the Medline® database. All phase III randomized trials and systematic reviews evaluating the role and modalities of RT in invasive BC were included, together with some noncontrolled studies if no randomized trials were identified. The quality and clinical relevance of the studies were evaluated to determine the level of evidence. RESULTS: The maximum delay between surgery and RT should ≤8 weeks when chemotherapy (CT) is not indicated. This should not exceed 24 weeks when adjuvant CT is administered. Whole breast RT delivering 50 Gy in 25 fractions followed by a boost of 10-16 Gy remains the standard of care after conservative surgery (CS). In the elderly population, for certain cases presenting comorbidities associated with a limited life expectancy, RT indication (even hypofractioned) and boost delivery may be unnecessary in the light of an unfavourable risk/benefit ratio. RT technique and indications should not vary in case of neoadjuvant CT followed by CS. After total mastectomy, RT should be indicated in N+ and in N- patients with high risk of local recurrence. The experts recommend to initiate tamoxifen at the end of RT, while aromatase inhibitors could be administered either concomitantly or sequentially with RT. There is no consistent data to delay (or suspend) trastuzumab administration during RT. As for all patients, in case of concurrent RT-trastuzumab administration, reduction of cardiac tissues exposure is highly recommended. After breast reconstruction, RT should be delivered as after standard CS without boost. CONCLUSION: Due to significant variations in practice in the treatment of patients with BC, our group aimed to provide guidelines for clinical practice. The systematic review of the literature formed the basis of our evidence-based recommendations; however expert agreements were necessary on those subjects that are still under debate. Our group will update these guidelines every 4 years, taking in consideration new advances in technology, new drugs administration, biologic tools and innovative therapeutic options.

Ductal carcinoma in situ of the breast in younger women: a subgroup of patients at high risk.

BACKGROUND: After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS. METHODS: From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy. RESULTS: 37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype (p = 0.004), histological size more than 10 mm (p = 0.011), necrosis (p = 0.022) and positive margin status (p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%. CONCLUSION: High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free.

Quality indicators in breast cancer care.

To define a set of quality indicators that should be routinely measured and evaluated to confirm that the clinical outcome reaches the requested standards, Eusoma has organised a workshop during which twenty four experts from different disciplines have reviewed the international literature and selected the main process and outcome indicators available for quality assurance of breast cancer care. A review of the literature for evidence-based recommendations have been performed by the steering committee. The experts have identified the quality indicators also taking into account the usability and feasibility. For each of them it has been reported: definition, minimum and target standard, motivation for selection and level of evidence (graded according to AHRO). In overall 17 main quality indicators have been identified, respectively, 7 on diagnosis, 4 on surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging, counselling, follow-up and rehabilitation. Breast Units in Europe are invited to comply with these indicators and monitor them during their periodic audit meetings.

[Ductal carcinoma in situ of the breast (DCIS). Histopathological features and treatment modalities: analysis of 1,289 cases]. / Carcinomes canalaires in situ (CCIS). Caractéristiques histopathologiques et traitement : analyse de 1 289 cas.

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.