Risk factors for breast fibrosis and unfavorable cosmetic outcomes after breast conserving therapy in the contemporary treatment era: a systematic review.

[BACKGROUND] This systematic review aimed to identify risk factors for fibrosis and unfavorable cosmetic outcomes after breast conserving therapy (BCT) for breast cancer in the light of contemporary oncoplastic surgery and 3D-radiotherapy techniques.

[METHODS] The systematic literature search was carried out in Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and CINAHL. Studies published after 2005, reporting two or more risk factors for fibrosis or unfavorable cosmetic outcomes as primary outcomes were eligible for inclusion. Only prospective studies with 100 or more patients analyzed were included. The Quality In Prognosis Studies tool and Cochrane risk-of-bias tool were used to assess risk of bias. Patient, tumor, and treatment-related predictors were identified.

[RESULTS] Twelve papers investigating 12.118 patients were identified. Risk factors for both the development of fibrosis and unfavorable cosmetic outcomes were increasing age, larger tumor size, re-resection, poor early cosmetic outcomes before the start of radiotherapy, high boost dose, boost volume per 10 cc, homogeneity-index, dose whole breast irradiation, and adjuvant chemotherapy. No specific risk factors in the setting of BCT with complex oncoplastic surgery techniques or ultra-hypo fractionated radiotherapy were identified in this review.

[CONCLUSION] The risk factors identified in this review are largely similar to those found in 2D-radiotherapy studies; dose homogeneity was additionally identified. Administering chemotherapy before radiotherapy should be considered for patients requiring both treatments. However, the lack of sufficient high-quality data regarding BCT with (complex) oncoplastic surgery techniques and ultra-hypo fractionated radiotherapy schedules address the need for large, multidisciplinary prospective studies with long-term follow-up.