Radiation therapy of the primary tumour and oligometastatic sites in patients with breast cancer with synchronous metastases: A literature review.

De novo metastatic breast cancer represents 5 to 8% of all breast cancers (2500 new cases per year in France). Systemic treatment is the cornerstone of treatment, whereas radiation therapy usually has a palliative intent. Advances in systemic and local treatments (surgery and radiation therapy) have substantially improved overall survival. In the recent breast cancer statistics in the United States, the 5-year relative survival for patients diagnosed during 2012-2018 was 29% for stage IV (Breast Cancer Statistics). Thus, an increasing proportion of metastatic breast cancers present a prolonged complete response to systemic therapy, which raises the question of the impact of local treatment on patient survival. Radiation therapy has shown its value for early breast cancer, but its place in the local management of the primary tumour or oligometastatic sites for de novo metastatic breast cancer remains under debate. This article is a literature review assessing the role of radiation therapy directed to the primary tumour and oligometastatic sites of breast cancer in patients with synchronous metastases, in order to highlight clinicians in their therapeutic decision.

Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer.

BACKGROUND: To improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases (BM) from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population. PATIENTS AND METHODS: This phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal BMs from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy × 10-30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m(2)/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability. RESULTS: Between February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 years (29-79). Median follow-up was 9.4 months [1.0-68.1]. ORRs at 6 weeks were 36% in the WBRT arm and 30% in the WBRT + TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common ≥grade 2 acute toxicity was reversible lymphopenia. CONCLUSION: WBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. CLINICALTRIALS.GOV: NCT00875355.

[Indication of radiotherapy after neoadjuvant chemotherapy in breast cancer]. / Place de la radiothérapie après chimiothérapie première dans le cancer du sein.

Indications for adjuvant radiotherapy in breast cancer are defined from the clinical data and the pathological extent of disease in the surgical specimen. Neoadjuvant chemotherapy could modify the pathological characteristics of the tumour, inducing a pathologic complete response in 15 to 50% of cases, challenging the classical indications of adjuvant radiotherapy. The benefit of adjuvant radiotherapy after neoadjuvant chemotherapy was not prospectively evaluated. Nonetheless, from retrospective series, some recommendations with a low level of proof could be given: (i) after lumpectomy, radiotherapy of the mammary gland must be performed even in case of pathologic complete response; (ii) after mastectomy, postoperative radiotherapy is recommended in case of cT3-T4, cN1-3 (clinical or radiological) or pathologically involved nodes; (iii) irradiation of the lymph nodes areas is more questionable, but could be also proposed in case of cN1 or pN1. These recommendations are in accordance with those recently published by the National Cancer Institute and the French National Cancer Institute.

[Breast conserving surgery in locoregional treatment of breast carcinoma after Hodgkin lymphoma]. / Traitement conservateur dans la prise en charge locorégionale du cancer du sein après lymphome de Hodgkin.

PURPOSE: To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. PATIENTS AND METHODS: Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. RESULTS: Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). CONCLUSIONS: Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position.

[Role of locoregional radiation therapy in breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy. The Institut Curie-Hôpital René-Huguenin experience]. / Rôle de l'irradiation locorégionale adjuvante en l'absence d'envahissement ganglionnaire après chimiothérapie néoadjuvante, mastectomie totale et lymphadénectomie axillaire pour un cancer du sein. Expérience de l'hôpital René-Huguenin-institut Curie.

PURPOSE: Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease and challenges the standard indications of adjuvant postmastectomy radiation therapy. We retrospectively evaluated the impact of postmastectomy radiation therapy in breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy. PATIENTS AND MATERIALS: Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 134 patients had pN0 status after neoadjuvant chemotherapy and mastectomy. Demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The impact of postmastectomy radiation therapy on locoregional recurrence-free survival and overall survival was evaluated by multivariate analysis including known prognostic factors. RESULTS: Among 134 eligible patients, 78 patients (58.2%) received postmastectomy radiation therapy, and 56 patients (41.8%) did not. With a median follow-up time of 91.4 months, the 10-year locoregional recurrence-free survival and overall survival rates were 96.2% and 77.2% with postmastectomy radiation therapy and 86.8% and 87.7% without radiation therapy, respectively (no significant difference). In multivariate analysis, there was a trend towards poorer overall survival among patients who did not have a pathologically complete primary tumour response after neoadjuvant chemotherapy (hazard ratio [HR], 6.65; 95% CI, 0.82-54.12; P=0.076). Postmastectomy radiation therapy had no effect on either locoregional recurrence-free survival (HR, 0.37; 95% CI, 0.09-1.61; P=0.18) or overall survival (HR, 2.06; 95% CI, 0.71-6; P=0.18). There was a trend towards poorer overall survival among patients who did not have pathologically complete in-breast tumour response after neoadjuvant chemotherapy (HR, 6.65; 95% CI, 0.82-54.12; P=0.076). CONCLUSIONS: This retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence or death when postmastectomy radiation therapy was omitted in breast cancer patients with pN0 status after neoadjuvant chemotherapy and mastectomy. Whether the omission of postmastectomy radiation therapy is acceptable for these patients should be addressed prospectively.

Treatment of the primary tumor in breast cancer patients with synchronous metastases.

Data from the Surveillance, Epidemiology, and End Results program and the European Concerted Action on survival and Care of Cancer Patients (EUROCARE) project indicate that approximately 6% of women newly diagnosed with breast cancer have stage IV disease, representing approximately 12 600 new cases per year in the United States in 2005. Historically, local therapy of the primary tumor in this setting has been aimed solely at symptom palliation. However, several studies suggest that surgical excision or exclusive irradiation of the primary tumor can prolong these patients' survival. In contrast, the impact of surgical dissection of regional lymph nodes and postoperative radiotherapy is poorly documented, and the patient subgroups most likely to benefit from treatment of the primary tumor remain to be identified. Two prospective studies are currently examining the benefits of locoregional therapy compared with systemic therapy alone in this setting. Here, we discuss current issues regarding treatment of the primary tumor in breast cancer patients with synchronous metastases.

[Histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma]. / Chimioradiothérapie préopératoire des adénocarcinomes du pancréas: évaluation anatomopathologique de l'efficacité thérapeutique.

PURPOSE: Several phase II studies have shown the feasibility of neoadjuvant chemoradiation regimens for resectable localized pancreatic adenocarcinoma. However, there is to date no completed phase III study to validate this approach and treatment effects evaluation still remains an active area of investigation. From the mature results of the SFRO-FFCD 9704 trial, we explored the antitumoral effect of a 5-fluoro-uracil and cisplatin-based preoperative chemoradiation regimen, with a special highlight on the histopathological response and performed a literature review. PATIENTS AND METHODS: Treatment consisted of concurrent radiotherapy (50 Gy within five weeks) and chemotherapy with 5-fluoro-uracil (300 mg/m(2)/day, five days/week, weeks 1-5) and cisplatin (20mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumour in patients without progression. RESULTS: In all, 41 patients were enrolled, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (≥ 80% of severely degenerative cancer cells), with one complete pathologic response. The local recurrence and two-year survival rates were 4 and 32%, respectively, for the 26 operated patients. CONCLUSION: Our results suggest that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neoadjuvant chemoradiation may serve as a surrogate marker for treatment efficacy and further research is needed to determine new prognostic and predictive factors of treatment response.

[Role of lymph node irradiation in breast cancer patients with negative pathologic node status after neoadjuvant chemotherapy: the René-Huguenin Cancer Center experience]. / Rôle de l'irradiation ganglionnaire chez les patientes indemnes d'envahissement ganglionnaire après chimiothérapie néoadjuvante pour un cancer du sein: expérience du centre René-Huguenin.

PURPOSE: Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery. PATIENTS AND MATERIALS: Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival. RESULTS: All 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR]=3.05; 95% CI, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR]=2.24; 95% CI, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival. CONCLUSIONS: Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study.

[National breast cancer brachytherapy survey in France: Results and perspectives in 2009]. / Enquête nationale sur la curiethérapie dans le cancer du sein : état des lieux et perspectives en 2009.

PURPOSE: To present the national survey patterns in France for breast cancer brachytherapy in 2009. MATERIAL AND METHOD: A written questionnaire was sent to the academic and general hospitals and the anticancer centres. The different items were type of institution; breast cancer clinical trial participation; number of breast brachytherapy per year; its indications; material and dose rate used. RESULTS: Among the 76 sent questionnaires, 35 (46 %) answers were available: 9 % of academic hospitals and 50 % of cancer centres performed breast brachytherapy. The number of breast brachytherapy per year ranged between 300 and 350. The indications were boost (100 %), partial breast irradiation (20 %) and second conservative treatment for local recurrence (53 %). The implanted material consisted in needles (27 %) and plastic tubes (73 %). The dose rate was low (50 %), pulsed (25 %) and high (25 %). CONCLUSION: Breast brachytherapy appears as a validated technique in case of boost but remains under investigation for partial breast irradiation and second conservative treatments. Good clinical practice rules as well as technical and dosimetric guidelines are needed. A cost-effective analysis of breast brachytherapy is warranted.

Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review.

BACKGROUND: We explored the feasibility and the histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks) and chemotherapy with 5-fluorouracil (300 mg/m(2)/day, 5 days/week, weeks 1-5) and cisplatin (20 mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. RESULTS: In all, 41 patients were enrolled; 38 (93%) received >or=47 Gy; 30 patients (73%) received >or=75% of the prescribed doses of chemotherapy. Among 40 assessable patients, 27 (67.5%; 95% confidence interval 50.9% to 81.4%) were successfully treated (entire dose of radiation, >or=75% of the chemotherapy dose, no grade 4 non-hematologic toxicity). In all, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (>or=80% of severely degenerative cancer cells), with one complete pathologic response. Operative mortality was 2.8%. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. CONCLUSIONS: This proposed preoperative scheme is feasible, does not prevent successful surgery, and provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate.