Our analyses indicate that the risks of early and late radiogenic lung sequelae are strongly related to the age of the patient, the volume of the irradiated lung, and the dose to it.

Fulvestrant is a pure estrogen receptor (ER) antagonist approved for the treatment of metastatic ER positive breast cancer in postmenopausal women with disease progression following antiestrogen therapy. The clinical results of fulvestrant demonstrated encouraging activity in tumors in spite of HER2 positivity, but data about its use after progression on anti-HER2 agents are limited. Partial responses and durations of response of 12, 25, and 38 months in three cases with multiple metastases of ER positive and HER2 positive breast cancer were observed; all patients had been treated with 1–4 regimens of an anti-HER2 agent in combination with chemotherapy or an aromatase inhibitor before the initiation of fulvestrant. Fulvestrant is a valuable option with limited toxicity and durable response in metastatic HER2 and ER positive breast cancer after progression on anti-HER2 agents as well. Therapeutic benefit even in extensive skin metastases and (irradiated) brain metastases may be expected. Further investigations are warranted to establish where it fits into the multimodal management of ER and HER positive breast cancer.

There is a need for the selection of those breast cancers where benefit may be attained from the addition of an anthracycline to the adjuvant chemotherapy. The expression of topoisomerase II alpha (TOP2A) protein in 3 cohorts of breast cancers treated with adjuvant dose-dense anthracycline-based chemotherapy was determined retrospectively. The TOP2A status was analysed in relation with the other standard tumour features and the outcome. TOP2A IHC results were assessable in 106 patients: with a cut-off value of 15%, 48% of the tumours were classified as TOP2A-positive. The expression of TOP2A correlated with that of Ki67 (R = 0.532, p < 0.001) and a high grade (p = 0.04), but did not correlate with the proportion of ER- or PR-positive cells in the tumour. More tumors were TOP2A-negative among the ER- or PR-positive cancers than among the ER/PR-negative cancers (p = 0.021 and p = 0.002, respectively). After a median follow-up time of 64.5 months, 31 relapses (23.5%) and 23 deaths (17.4%) had occurred in 131 patients. The overall survival was longer in the TOP2A-positive cases than in the TOP2A-negative cases. The recurrence-free survival and the overall survival were significantly more favourable in the ER/PR-negative and TOP2A-positive tumours than in other subgroups. In a Cox proportional hazards model, the grade and TOP2A remained significant determinants in the ER/PR-negative subgroup. TOP2A positivity and grade 3 indicated a decrease in the risk of death with HR = 0.211 (95% CI: 0.042-1.05, p = 0.056) and HR = 0.216 (95% CI: 0.047-0.990, p = 0.048), respectively. A higher sensitivity to anthracycline-containing regimens is suggested in ER/PR-negative and TOP2A-positive cancers.

BackgroundProne positioning for breast radiotherapy is preferable when the aim is a reduction of the dose to the ipsilateral lung or the heart in certain left-sided cases.Materials and methodsIn 100 breast cancer cases awaiting postoperative whole-breast radiotherapy, conformal radiotherapy plans were prospectively generated in both prone and supine positions. The axillary nodal region (levels I–III) and internal mammary (IM) lymph-node region in the upper three intercostal spaces were retrospectively contoured. The mean doses to the nodal regions and the volume receiving 25 Gy (V25Gy), V45Gy, and V47.5Gy were compared between the two treatment positions.ResultsIn most cases, the doses to axillary levels I–III and the IM lymph nodes were inadequate, regardless of the treatment position. The nodal doses were significantly lower in the prone than in the supine position. The radiation doses to levels II–III and IM nodes were especially low. The V45Gy and V47.5Gy of the level I axillary lymph nodes were 54.6% and 40.2%, respectively, in the supine, and 3.0% and 1.7%, respectively, in the prone position. In the supine position, only 17 patients (17%) received a mean dose of 45 Gy to the axillary level I nodes.ConclusionThe radiation dose to the axillary and IM lymph nodes during breast radiotherapy is therapeutically insufficient in most cases, and is significantly lower in the prone position than in the supine position.

Adjuvant radiotherapy should be based on individual risk-benefit features. The need of the introduction of special techniques may be decided after the dose-volume analysis of the conformal radiotherapy plan based on 3D radiation treatment planning.