ABSTRACT
BACKGROUND: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting. PATIENTS AND METHODS: Data of 146 patients with stages II-III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients. RESULTS: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade >/=2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity. CONCLUSION: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects.
Subject(s)
Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Radiotherapy, Adjuvant/adverse effects , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Combined Modality Therapy/adverse effects , Dermatitis/etiology , Esophagitis/etiology , Female , France , Humans , Mastectomy , Middle Aged , Receptor, ErbB-2/metabolism , TrastuzumabABSTRACT
Trastuzumab (Herceptin) is the first humanised monoclonal antibody targeting the HER2 antigen in breast cancer. HER2 receptor has been individualised 20 years ago. During the past 10 years, trastuzumab administration has radically modified the prognosis of the patients that are treated for HER2 positive breast cancer. Its efficacy has been demonstrated in the metastatic and adjuvant settings. While, trastuzumab based-regimens became the standard of care in the treatment of HER2/neu positive breast cancer, the optimal combination (concurrently or sequentially) to chemotherapy and radiation therapy is still unknown. Indeed, while the concurrent administration of trastuzumab and anthracyclines is not recommended because of a high risk of cardiac toxicity, there is no published data on the best sequence of trastuzumab and radiation therapy administration, particularly when internal mammary chain is involved. The benefit/risk ratio of the concurrent and sequential administration of trastuzumab with chemotherapy and radiation therapy will be discussed in this review.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Animals , Anthracyclines/administration & dosage , Anthracyclines/adverse effects , Anthracyclines/therapeutic use , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Combined Modality Therapy , Disease Models, Animal , Female , Follow-Up Studies , Heart/drug effects , Humans , Multicenter Studies as Topic , Radiotherapy Dosage , Radiotherapy, Adjuvant , Randomized Controlled Trials as Topic , Receptor, ErbB-2 , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Trastuzumab , Treatment OutcomeABSTRACT
OBJECTIVES: In a retrospective study of bilateral Ductal Carcinoma In Situ (DCIS), cases were analysed to determine the relationship between the two events. MATERIAL AND METHODS: From 1971 to 2001, among 812 patients with DCIS in Bergonie Institute, 78 suffering from bilateral DCIS and only19 were treated entirely in our institute. It was either synchronous DCIS or asynchronous (before 6 months). We realised a comparative study between, clinical and pathological characteristics of each DCIS. RESULTS: In case of asynchronous DCIS, contra lateral DCIS occurred after a median 75-months period and until 22 years after the first event. We found at least for one histological subtype an agreement in 53% of cases. In 31% of cases, the grade was the same. For low plus intermediary grade versus high grade, the agreement was 53%. There was a subtype and grade agreement of 32% and a subtype or grade agreement in 63% of cases. CONCLUSION: Histological agreement between the two lesions indicated the possible existence of in situ bilateral disease in these women. The local relapse rate was 20% and all of them were invasive. The risk of relapse in controlateral breast is high and patient needs a long follow up even in case of mastectomy.