Neoadjuvant Radio(chemo)therapy for Breast Cancer: An Old Concept Revisited.

BACKGROUND: The international standard of care for the treatment of high-risk breast cancer (BC) consists of neoadjuvant chemotherapy (NACT) and surgery followed by adjuvant whole breast/chest wall irradiation. In this setting, the time interval from the start of NACT to the end of radiotherapy (RT) is usually postponed to 6 months or longer. In addition to this, a high percentage of capsular fibrosis may occur when breast implants are irradiated. Most of these disadvantages could be avoided by using preoperative RT (PRT). PRT is already the standard of care in several other tumor entities (rectal cancer, esophagus carcinoma, lung cancer, and soft tissue sarcoma). Nevertheless, PRT in BC has been tested in several trials, but randomized prospective trials using modern radiation technology and systemic therapies are lacking. The available evidence summarized in this review indicates that PRT may improve survival and reduce long-term toxicity in patients with a higher risk of recurrence and should be consequently tested in a randomized trial. SUMMARY: Prospective, randomized trials concerning PRT in high-risk BC are needed. We plan to conduct a NeoRad trial (NACT followed by PRT in high-risk BC). KEY MESSAGES: Prospective, randomized studies concerning PRT in high-risk BC are needed.

Recent advances in radiotherapy of breast cancer.

Radiation therapy is an integral part of the multidisciplinary management of breast cancer. Regional lymph node irradiation in younger trials seems to provide superior target coverage as well as a reduction in long-term toxicity resulting in a small benefit in the overall survival rate. For partial breast irradiation there are now two large trials available which support the role of partial breast irradiation in low risk breast cancer patients. Multiple randomized trials have established that a sequentially applied dose to the tumor bed improves local control with the cost of worse cosmetic results.

Long-term quality of life after preoperative radiochemotherapy in patients with localized and locally advanced breast cancer.

BACKGROUND: Preoperative radiotherapy (PRT) or radiochemotherapy (PRCT) is used in different tumor sites. The aim of the study was to examine the long-term quality of life (QoL) of localized / locally advanced breast cancer patients treated with PRT/PRCT followed by breast-conserving surgery (BCS) or mastectomy (ME). METHODS: Assessment of QoL was done using EORTC QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. The summary scores were categorized into 4 distinct groups to classify the results. Furthermore, a comparative analysis was performed between the study cohort and a previously published reference cohort of healthy adults. We assessed the impact of different clinical, prognostic, and treatment-related factors on selected items from C30 and BR23 using a dependence analysis. RESULTS: Out of 315 patients treated with PRT/PCRT in the years 1991 to 1999, 203 patients were alive at long-term follow-up after a mean of 17.7 years (range 14-21). 37 patients were lost to follow-up and 61 patients refused to be contacted, leading to 105 patients (64 patients after BCS and 41 after ME) being willing to undergo further clinical assessment regarding QoL outcome. Overall, QoL (QLQ-C30) was rated "excellent" or "good" in 85% (mean value) of all patients (BCS 83%, ME 88%). Comparative analysis between the study cohort and a published healthy control group revealed significantly better global health status and physical and role functioning scores in the PRT/PRCT group. The analysis demonstrates no differences in nausea/vomiting, dyspnea, insomnia, constipation, or financial difficulties. According to the dependence analysis, global QoL was associated with age, operation type and ME reconstruction. CONCLUSION: We did not detect any inferiority of PRT/PRCT compared to a healthy reference group with no hints of a detrimental long-term effect on general and breast-specific quality of life.

Long-term cosmetic outcome after preoperative radio-/chemotherapy in locally advanced breast cancer patients.

BACKGROUND: Preoperative radiotherapy and chemoradiotherapy (PRT/PCRT) represent an increasingly used clinical strategy in different tumor sites. We have previously reported on a PRT/PRCT protocol in patients with locally advanced non-inflammatory breast cancer (LABC) with promising clinical results. However, concerns regarding a possible unfavorable influence on cosmesis still exist. Thus, the aim of the current study was to examine long-term cosmetic outcome in our series of LABC patients treated with PRT/PCRT followed by breast-conserving surgery (BCS) or mastectomy (ME). PATIENTS AND METHODS: Of the 315 patients treated with PRT/PCRT in the years 1991 to 1999, 203 were still alive at long-term follow-up of mean 17.7 years (range 14-21). Thirty-seven patients were lost to follow-up and 58 patients refused to be contacted, which resulted in 107 patients (64 patients after BCS and 43 after mastectomy) being available and willing to undergo further cosmetic assessment. One patient had a complete response after PRT/PCRT and refused surgery. PRT/PCRT consisted of external beam radiation therapy (EBRT) with 50 Gy (5â€¯× 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with a consecutive electron boost or (in case of BCS) a 10-Gy interstitial brachytherapy boost with Ir-192 prior to EBRT. Overall, chemotherapy was administered either prior to RT or concomitantly in the majority of patients. BCS and mastectomy were performed with and without reconstruction. The cosmetic outcome was assessed by patient questionnaire, panel evaluation, and breast retraction assessment (BRA) score. RESULTS: Eighty percent of all BCS patients rated their overall cosmetic result as "excellent" or "good" as compared to 55.8% after mastectomy. Patient and panel ratings on cosmetic outcomes were similar between the two groups. No grade III or IV fibrosis were detected in any of the groups. The median BRA score after breast conserving surgery was 2.9. CONCLUSION: PRT/PCRT is associated with low grades of fibrosis and a good to excellent long-term cosmetic outcome.

Implant-based breast reconstruction using a titanium-coated polypropylene mesh (TiLOOP Bra): a multicenter study of 231 cases.

BACKGROUND: An alternative to implant-based breast reconstruction using acellular dermal matrix is the use of a titanium-coated polypropylene mesh. The mesh was approved for implant-based breast reconstruction in Europe in 2008, but only limited clinical data are available. METHODS: Two hundred seven patients (231 breasts) with skin-sparing/nipple-sparing or modified radical mastectomy and immediate or delayed implant-based breast reconstruction using titanium-coated polypropylene mesh were evaluated retrospectively. The primary endpoints were identification of patient-related and surgical factors that were predictive for an adverse outcome and the development of recommendations for patients eligible for implant-based breast reconstruction using the mesh. Complications were divided into major (need for additional surgery), minor (conservative treatment), and implant loss. Univariate and multivariate logistic regression analyses were performed to determine the influence of the patient- and procedure-related characteristics on postoperative complications and implant loss. RESULTS: No risk factors were observed for patient-associated complications. Major complications occurred in 13.4 percent, minor complications in 15.6 percent, and implant loss in 8.7 percent of patients. Univariate analysis revealed procedure-related risk factors for postoperative complications with a bilateral procedure (p = 0.013) or skin expansion before implant surgery (p = 0.043). Multivariate analysis confirmed these risk factors and revealed an increased risk for implant loss in patients with skin necrosis (p < 0.001) and capsule fibrosis (p < 0.001). CONCLUSIONS: This titanium-coated polypropylene mesh shows acceptable complication rates and can be a helpful device in implant-based breast reconstruction. The mesh should only be used in primary cases and, when adhering to the proposed indications, is a safe and convenient option in implant-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Skin-sparing mastectomy and immediate reconstruction with DIEP flap after breast-conserving therapy.

BACKGROUND: Currently about 70% of women who suffer from breast cancer undergo breast-conserving therapy (BCT) without removing the entire breast. Thus, this surgical approach is the standard therapy for primary breast cancer. If corrections are necessary, the breast surgeon is faced with irritated skin and higher risks of complications in wound healing. After radiation, an implant-based reconstruction is only recommended in selected cases. Correction of a poor BCT outcome is often only solved with an additional extended operation using autologous reconstruction. MATERIAL/METHODS: In our plastic surgery unit, which focuses on breast reconstruction, we offer a skin-sparing or subcutaneous mastectomy, followed by primary breast reconstruction based on free autologous tissue transfer to correct poor BCT outcomes. Between July 2004 and May 2011 we performed 1068 deep inferior epigastric artery perforator (DIEP) flaps for breast reconstruction, including 64 skin-sparing or subcutaneous mastectomies, followed by primary DIEP breast reconstruction procedures after BCT procedures. RESULTS: In all free flap-based breast reconstruction procedures, we had a total flap loss in 0.8% (9 cases). Within the group of patients after BCT, we performed 41 DIEP flaps and 23 ms-2 TRAM flaps after skin-sparing or subcutaneous mastectomies to reconstruct the breast. Among this group we had of a total flap loss in 1.6% (1 case). CONCLUSIONS: In cases of large tumour sizes and/or difficult tumour locations, the initial oncologic breast surgeon should inform the patients of a possibly poor cosmetic result after BCT and radiation. In our opinion a skin-sparing mastectomy with primary breast reconstruction should be discussed as a valid alternative.

Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers.

PURPOSE: To estimate the risk for contralateral breast cancer in members of BRCA1- and BRCA2-positive families and to determine predictive risk factors. PATIENTS AND METHODS: A retrospective, multicenter, cohort study was performed from 1996 until 2008 and comprised 2,020 women with unilateral breast cancer (index patients, n = 978; relatives, n = 1.42) from 978 families who had a BRCA1 or BRCA2 mutation. Cox regression analysis was applied to assess the association of age at first breast cancer with time from first to contralateral breast cancer, stratified by the affected BRCA gene. RESULTS: The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer than members of families with BRCA2 mutations. Younger age at first breast cancer was associated with a significantly higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95% CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer developed contralateral breast cancer, compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50 years of age at first breast cancer. CONCLUSION: Contralateral breast cancer risk depends on age at first breast cancer and on the affected BRCA gene, and this risk should be considered in treatment planning.