| Background Breast cancer is one of the most common cancers in women and the most common causes of death in women with cancer around the world. About 12 percent (nearly 1/8) of women will become breast cancer patients in their lifetime. There will be a breast cancer patient in per 69 40-year-old women after ten years. In recent years, the incidence of breast cancer in Asia rose sharply and was narrowing the gap between North America and other regions. January 25,2016, Chinese Academy of Medical Sciences, National Cancer Institute and the National Cancer Registration Center reported Chinese cancer statistics in 2015 in the CA magazine, showing that breast cancer is the most common cancer among Chinese women. Breast cancer accounted for 15% of all Chinese female cancers. Breast cancer incidence is growing at a rate of 3%-4% per year in China and 7.5% in the urban. In the developed eastern coastal areas of China, there was a breast cancer patient in per 1,000 women. Breast cancer has become a threat to women’s health.To date, surgery is still the main therapy for breast cancer. In 1980, Watts et al firstly describe nipple-sparing mastectomy (NSM), which additionally preserved nipple-areola complex (NAC), aiming at improving the mental and aesthetics results. Patient surveys had proved satisfaction with reservation of NAC consistently. American Cancer Database reported a 202% increase in patients undergoing NSM from 2005 to 2009. With the increasing number of recent articles demonstrating a safe oncologic outcome of NSM, the most recent NCCN guidelines (version 3.2015) recommended that NSM may be an alternative in carefully selected breast cancer patients managed by an experienced multidisciplinary team for biologically favorable, early-stage, invasive cancers and/or DCIS that located peripherally in the breast,>2cm from nipple. However, the indications for NSM have not reached any consensus. It is essential to recognize candidates for NSM by identifying the pedictors of occult NAC involvement.Currently, a variety of factors have been described to be associated with occult NAC involvement in breast cancer patients, but there is no consensus across studies and the data are conflicting. Therefore, a meta-analysis was conducted to pool the existing published literature, with hopes of potentially identifying parameters for patients who may be at higher risk for occult NAC involvement. In addition to occult NAC involvement, surgeons also pay great attention to local recurrence (LR) in the patients accepting NSM. There was few reported predictor of local recurrence accepting NSM. In this study we also performed a systematic review focuses on the impact of TND on local recurrence in the setting of NSM.Some retrospective studies but few prospective studies explored the impact of TND on occult NAC involvement in breast cancer patients. Besides, previous pathological examination just took one single block from nipple, resulting in certain one-sidedness. Studies have shown that one single block from nipple would miss some cases of occult NAC involevement. The whole NAC should be taken into several blocks for pathological examination, guaranteeing comprehensive view of the situation of NAC involvement. So we conducted a prospective study to investigate the impact of TND by peoperative imaging examination on occult NAC involvement in breast cancer patients to select suitable patients for NSM.Methods A systematic search irrespective of language was conducted through PubMed, Web of Science, Cochrane Library, CNKI and CBM datebases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. There was no restriction of publication dates, until October 1,2015. Studies reporting on the association of TND, tumor size, patient age, pathological features, lymph node status, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and multicentricity and occult NAC involvement in the setting of mastectomy were included in the meta-analysis. We performed a study-level meta-analysis using the statistical software Revman 5.3. Studies reporting on TND or multicentricity and LR in the setting of NSM were included in the systematic review. We performed the systematic review and calculate LR in different groups of different indacations about TND for NSM using the statistical software MetaAnalyst. Patients who received radical mastectomy for breast cancer without clinical NAC involvement were considered eligible for the present study. We measured TND by peoperative imaging examination and specimens. Cut NAC complete removed into 10-12 Slices, routinely embedded in formalin and made into HE slices. We investigated the impact of TND by peoperative imaging examination on occult NAC involvement by chi-square test, seting P<0.05 as statistically difference. And we compare TND by peoperative imaging examination and pathological examination by t-test, seting P<0.05 as statistically difference. Calculate the sensitivity, specificity, positive predictive value and negative predictive value of prediction of occult NAC involvement according to TND.Results In the meta-analysis about risk factors for occult NAC involvement, 1544 articles were identified from electronic search of databases and 11 clinical studies met the inclusion and exclusion criteria. The Relative Risk (RR) of "TND <xcm versus TND>xcm" was 2.41 (95% CI=2.41-4.01), P<0.00001. Smaller TND will significantly improve the risk of occult NAC involvement. In the subgroup analysis, The RR value for the group of "TND<1cm versus TND>1cm", "TND <2cm versus TND>2cm", "TND<3cm versus TND>3cm" and "TND<4cm versus TND>4cm" was 7.95 (95%CI=1.88-33.69),3.79 (95%CI=2.14-6.74),2.71 (95%CI=1.96-3.74) and 3.43 (95%CI=1.94-6.07) respectively. The weight average RRs of four groups were all statistically significant. Of note, the highest RR was discovered in the group of "TND<1cm versus TND>lcm". The Relative Risk (RR) of "T<xcm versus T>xcm" was 0.39 (95% CI=0.33-0.46), P<0.00001.Larger tumor will significantly improve the risk of occult NAC involvement. In the subgroup analysis, The RR value for the group of "T<2cm versus T>2cm", "T<2.5cm versus T>2.5cm", "T<5cm versus T>5cm" was 0.50(95% CI=0.38-0.65),0.33(95% CI= 0.26-0.41)and 0.26(95% CI=0.16-0.43) respectively. The weight average RRs of three groups were all statistically significant. Of note, the lowest RR was discovered in the group of "T<5cm versus T>5cm".The RR value of "Age<x versus age> x" was 1.27 (95% CI=0.92-1.75), P= 0.14. Age of patients was not associated with the risk of occult NAC involvement. The RR value of "lymph nodes positive versus negative" was 2.18 (95% CI= 1.84-2.57), P<0.00001. Positive lymph nodes will significantly improve the risk of occult NAC involvement. The RR value of "lymphovascular invasion vs noninvasion" was 2.13 (95% CI=1.34-3.37), P=0.001. Lymphovascular invasion will significantly improve the risk of occult NAC involvement. The RR value of "multicentric versus not multicentric" was 1.66 (95% CI=0.80-3.44), P=0.17. Multicentricity was not associated with the risk of occult NAC involvement.The RR value of "ER+versus ER-" was 0.78(95% CI=0.65-0.93), P=0.007. ER- will significantly improve the risk of occult NAC involvement. The RR value of "PR+versus PR-" was 0.72 (95% CI=0.60-0.87), P=0.0008.PR-will significantly improve the risk of occult NAC involvement. The RR value of "HER2+ versus HER2-" was 1.53 (95% CI=1.03-2.27), P=0.03. HER2+will significantly improve the risk of occult NAC involvement.The RR value of "histological Grade I versus Grade Ⅱ&Ⅲ" was 0.82 (95% CI= 0.62-1.08), P=0.16. The RR value of "histological Grade I&II versus Grade III" was 0.76 (95% CI=0.63-0.93), P=0.006. Histological Grade Ⅲ will significantly improve the risk of occult NAC involvement.In the system review about the impact of TND on local recurrence in the setting of NSM,1257 articles were identified from electronic search of databases and 8 clinical studies met the inclusion and exclusion criteria. A total of 123 patients of TND>lcm underwent NSM and were followed for a mean time of 23.3 months, while 319 patients of TND>2cm underwent NSM with a mean follow-up of 47.5 months. Studies with specific inclusion criteria of TND>1cm had a mean LR rate of 3.3% (95%CI=1.2%-8.4%) while those with a TND>2cm had a rate of 5.3% (95%CI=2.5%-11.1%).In the prospective study about the impact of TND by peoperative imaging examination on occult NAC involvement in breast cancer patients,29 patients with peformed modified radical mastectomy and 2 (7%) patients revealed occult NAC involvement by pathological examination. The average TND measured by peoperative imaging examination was 2.49±1.45 cm;the average TND measured by pathological examination was 2.92±1.40 cm. T-test showed TND measured by peoperative imaging examination was statistically less than which by pathological examination. p =0.04.There were 8 patients of TND≤1 cm, and 2 (25%) of them revealed occult NAC involvement. There were 21 patients of TND>1 cm and none of them revealed occult NAC involvement. Due to no positive event of TND>1 cm, chi-square test was not performed. The sensitivity, specificity, positive predictive value and negative predictive value of prediction of occult NAC involvement according to TND≤1 cm was 100%,78%,25% and 100% respectively.Conclusion Our meta-analysis showd that smalle TND (especially TND<1 cm), larger tumor size (especially T>5 cm), lymph node positive, estrogen receptor negative, progesterone receptor-negative, HER2-positive, lymphovascular invasion, histological Grade III significantly increases the risk of occult NAC involvement. But Age of paients and multicentricity were not associated with the risk of occult NAC involvement. Our systematic review showed that studies of TND >1cm and TND>2cm for NSM had mean LR of 3.3% and 5.3% respectively. Such low LR rates suggests that patient selection by experienced surgeons for patients with a TND>1cm or TND>2cm is safe oncologically. Our prospective study has shown that TND≤1 cm significantly increases the risk of occult NAC involvement. Based on evidences from three parts, in order to maximize the number of eligible patients for NSM as well as minimize the risk for NAC involvement and local recurrence, we recommend TND> 1cm and no clinical NAC involvement as indicaitons for NSM, meanwhile regarding risk factors of T> 5 cm, lymph node-positive, estrogen receptor negative, progesterone receptor-negative, HER2-positive, lymphovascular invasion, histological Grade Ⅲ, and frozen biopsy sub-nipple was needed in the procure of NSM. More large prospective studies with long-term follow-up would be necessary to support our conclusions. |
PDF Full Text Request