Prognosis of isolated locoregional recurrence after early breast cancer with immediate breast reconstruction surgery: a retrospective multi­institutional study.

BACKGROUND: The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population. METHODS: This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS). RESULTS: Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3 months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS. CONCLUSIONS: Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients.

Nipple-areolar complex malposition in breast reconstruction after nipple-sparing mastectomy: a multi-institutional retrospective observational study in Japan.

BACKGROUND: Position of the nipple-areolar complex (NAC) is an important factor in the esthetic impression of the breast, and NAC malposition is often an issue in breast reconstruction after nipple-sparing mastectomy (NSM). The purpose of this study was to evaluate the degree of NAC malposition depending on several factors using data quantified with the Mamma Balance application (Medic Engineering K.K., Kyoto, Japan). METHODS: Patients who underwent unilateral breast reconstruction after NSM at eight hospitals in Japan between 2007 and 2020 were retrospectively investigated. Using Mamma Balance, NAC malposition was quantified separately in horizontal and vertical directions using patient photographs from pre-operatively and 6-24 months post-operatively. The degree of malpositioning was then statistically compared using various factors. RESULTS: The NAC deviated more cranially and medially with implants than that with flaps. Cases with latissimus dorsi flap showed lateral malposition more often than cases with deep inferior epigastric artery perforator flap. With flaps, lateral incisions showed more lateral malposition, and peri-areolar incisions tended to show more medial NAC malposition. In cases with severe post-operative infection of the implant, the NAC tended to deviate cranially. In radiation cases, the NAC deviated cranially. No significant difference was observed according to the degree of breast ptosis or use of the pull-down operation. Only a very weak correlation was observed between a larger amount of mastectomy and more cranial NAC malposition with both flaps and implants. CONCLUSIONS: This study provides insights into the tendencies and characteristics of NAC malposition.

Impact of radiation therapy for breast cancer with involved surgical margin after immediate breast reconstruction: A multi-institutional observational study.

INTRODUCTION: Involved surgical margins are risk factors for local recurrence and re-excision is often difficult, particularly in patients with breast cancer undergoing immediate breast reconstruction (IBR). However, the magnitude of the effect of radiation therapy on preventing local recurrence for breast cancers with involved margins has not been sufficiently assessed. MATERIALS AND METHODS: We retrospectively assessed sites of involved surgical margins and local recurrence after mastectomy with IBR in patients with early breast cancer between 2008 and 2016. The effect of postoperative radiation therapy was evaluated in patients with involved margins, adjusted for nuclear grade, lymphatic invasion, surgical procedures, and primary systemic therapy. RESULTS: A total of 274 (5.8 %) out of 4726 patients who underwent mastectomy with IBR had involved surgical margins: 133, 68, 88, and 26 had involvement of the skin, deep margin, lateral margins, and nipple, respectively (including duplicates). Radiation therapy was administered to 54 patients with involved margins. In patients with involved margins, 7-year cumulative incidences of local recurrence were 1.9 % and 12.6 % with and without radiation therapy, respectively (adjusted hazard ratio, 0.17; 95 % CI, 0.04-0.80). Local recurrence occurred in 28 patients, and the sites were skin, subcutaneous tissue, muscle, and nipple-areola complex in 7, 17, 1, and 3 patients, respectively. Among them, 23 (82.1 %) were associated with involved margin sites. CONCLUSIONS: Radiation therapy meaningfully reduced the incidence of local recurrence in patients with breast cancer with margin involvement after mastectomy with IBR. Most local recurrences occurred at involved margin-related sites.

Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy.

BACKGROUND: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. METHODS: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. RESULTS: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74-1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. CONCLUSION: IBR after NAC is a safe procedure with an acceptable postoperative complication profile.

Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence.

BACKGROUND: Mastectomy has been the standard surgical treatment for ipsilateral breast tumor recurrence (IBTR). Recently, there has been growing interest in repeat breast-conserving surgery (rBCS) for IBTR among breast surgeons; however, there is currently little information regarding patient preferences for surgical procedure for IBTR. The purpose of this study was to evaluate preference for surgical procedure (mastectomy vs. rBCS) among breast cancer patients who had undergone salvage surgery for IBTR. METHODS: Overall, 100 breast cancer patients who had undergone salvage surgery for IBTR were asked about their preferred surgical methods for IBTR and the reason. The association of patient preference and the reasons related to various clinical and pathological factors were assessed. RESULTS: Of the 100 respondents, only 11 patients (11%) preferred rBCS. Patients who had undergone rBCS and radiotherapy for IBTR were significantly more likely to prefer to undergo rBCS than other groups (p = 0.030). The most frequent reason for choosing rBCS was the patient's desire to minimize breast deformity and surgical wounds. CONCLUSIONS: Our study revealed that there is a low rate of patients who opt to undergo rBCS among patients who had undergone salvage surgery for IBTR. Discrepancies in perceptions regarding the surgical procedure for IBTR between patients and their surgeons may exist.

The Japanese Breast Cancer Society Clinical Practice Guidelines for surgical treatment of breast cancer, 2022 edition.

The 2022 revision of the Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for surgical treatment of breast cancer was updated following a systematic review of the literature using the Medical Information Network Distribution Service (MINDS) procedure, which focuses on the balance of benefits and harms for various clinical questions (CQs). Experts in surgery designated by the JBCS addressed five areas: breast surgery, axillary surgery, breast reconstruction, surgical treatment for recurrent and metastatic breast cancer, and other related topics. The revision of the guidelines encompassed 4 CQs, 7 background questions (BQs), and 14 future research questions (FRQs). A significant revision in the 2022 edition pertained to axillary management after neoadjuvant chemotherapy in CQ2. The primary aim of the 2022 JBCS Clinical Practice Guidelines is to provide evidence-based recommendations to empower patients and healthcare professionals in making informed decisions regarding surgical treatment for breast cancer.

Ganglioside GD2 Expression Is Associated With Unfavorable Prognosis in Early Triple-negative Breast Cancer.

BACKGROUND/AIM: Gangliosides (acidic glycosphingolipids) have crucial regulatory roles in normal physiological processes, as well as in pathological conditions, including tumor onset and progression. GD2 is highly expressed in triple-negative breast cancer (TNBC), particularly in cancer stem cells. However, little is known on the clinical impact of GD2 expression on the prognosis of TNBC. Consequently, we aimed to investigate the association between GD2 expression in TNBC and the prognosis of TNBC. PATIENTS AND METHODS: We assessed GD2 expression in 76 patients with primary TNBC who had undergone surgery at our Institute between 2012 and 2015 using immunohistochemical analysis with a tissue microarray technique. We investigated the relationship between GD2 expression and clinicopathological factors in TNBC, recurrence-free survival (RFS), and overall survival (OS). RESULTS: Increased GD2 expression was observed in 45% of TNBC patients. There was no significant association between GD2 expression and clinicopathological factors in TNBC. The 5-year RFS rate among patients with GD2-positive TNBCs was significantly worse than that among patients with GD2-negative TNBCs (75.4% and 94.9%; HR=4.931; 95%CI=1.024-23.752; p=0.027). The OS in patients with GD2-positive TNBCs tended to be inferior to that of patients with GD2-negative TNBCs (HR=5.357; 95%CI=0.599-47.939; p=0.092). Interestingly, in patients with GD2-positive TNBCs, a higher grade of tumor-infiltrating lymphocytes (TILs) displayed a significantly better impact on OS (TILs-high vs. TILs-low; p=0.04). Both univariate and multivariate analyses showed that GD2 expression negatively affected RFS (p=0.027, p=0.021, respectively). CONCLUSION: GD2 expression is an independent unfavorable prognostic factor for TNBC.

Long-Term Outcomes of Breast Cancer Patients with Local Recurrence After Mastectomy Undergoing Immediate Breast Reconstruction: A Retrospective Multi-institutional Study of 4153 Cases.

BACKGROUND: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of, and factors associated with, local recurrence (LR) after IBR. METHODS: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. RESULTS: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p < 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p = 0.002). CONCLUSIONS: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR.

Preferences Regarding Breast Surgery Omission Among Patients With Breast Cancer Who Receive Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. PATIENTS AND METHODS: We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. RESULTS: Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). CONCLUSION: The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.

Long-term course of the changes in the nipple position after breast-conserving surgery.

PURPOSE: Even if favorable cosmetic outcomes are obtained shortly after breast-conserving surgery (BCS), cosmetic changes may occur up to several years after BCS. In the present study, we evaluated cosmetic changes while focusing on changes in the nipple position after BCS. METHODS: We examined the long-term course of changes in the nipple position over time after BCS using the proportion of the distance between the sternal notch and nipple (PDSN) in 196 patients. We also evaluated risk factors for long-term nipple position changes. RESULTS: The median follow-up period was 9.9 years. Nipple position changes occurred within eight years after BCS and seemed to plateau beyond that point. The body mass index (BMI), breast size, proportion of excision volume and axillary treatment were significantly associated with the nipple position changes within one to five years after BCS. The BMI, breast size, axillary treatment, chemotherapy and hormonal therapy were significantly associated with the nipple position changes within five to eight years after BCS. CONCLUSIONS: After BCS, the nipple position changes occur within about eight years. Obesity, large breast size, large excision volume, axillary treatment, chemotherapy and hormone therapy were factors that affected the treated breast shrinkage and increase in the left-right difference after BCS.

Physicians' perception about the impact of breast reconstruction on patient prognosis: a survey in Japan.

BACKGROUND: One barrier to the widespread use of breast reconstruction (BR) is physicians' perception that BR adversely affects breast cancer prognosis. However, there is limited information regarding physicians' understanding of the impact of BR on patient prognosis and which physicians have misunderstandings about BR. METHODS: We conducted an e-mail survey regarding the impact of BR on the prognosis of patients with breast cancer among members of the Japanese Breast Cancer Society. RESULTS: Of 369 respondents, 99 (27%) said that they believe BR affects patient prognosis. Female respondents and those who treat fewer new breast cancer patients per year were more likely to state that they believe BR affects patient prognosis (P = 0.006 and 0.007). Respondents who believed that BR affects patient prognosis underestimated 5-year overall survival rates in patients who receive BR and subsequently have local or regional recurrence in different sites. CONCLUSION: Our survey demonstrated that a quarter of respondents believe that BR affects patient prognosis and underestimate survival rates in patients who receive BR and have subsequent local or regional recurrence. Because of the lack of evidence regarding the impact of BR on patient prognosis, educating physicians by providing accurate knowledge regarding BR and patient prognosis is highly recommended.

Classification of Local Recurrence After Nipple-Sparing Mastectomy Based on Location: The Features of Nipple-Areolar Recurrence Differ from Those of Other Local Recurrences.

BACKGROUND: Little information is available about the clinical and pathologic characteristics of local recurrence (LR) after nipple-sparing mastectomy according to the locations of LR. METHODS: This study classified 99 patients into the following two groups according to the location of LR after nipple-sparing mastectomy: nipple-areolar recurrence (NAR) group and other locations of LR (oLR) group. The study evaluated whether the location of LR was associated with disease-free survival (DFS) after LR resection. RESULTS: For about half of the patients (44.4 %) with NAR, the primary cancer was estrogen receptor (ER)-negative and human epidermal growth factor receptor 2 (HER2)-positive. Conversely, in most of the patients with oLR (79.2 %), the primary cancer was ER-positive and HER2-negative. Among the LR tumors, the frequency of noninvasive carcinoma in the NAR tumors was significantly higher than in the oLR tumors (51.9 % vs 4.2 %, respectively). During a median follow-up period of 46 months, the location of LR was not associated with DFS after LR. In the NAR group, the presence or absence of LR tumor invasiveness was the only factor associated with DFS. In the oLR group, age at primary surgery was the only factor associated with DFS. CONCLUSION: This multi-institutional retrospective study demonstrated that the features of NAR, such as the characteristics of the primary and recurrent tumors and the prognostic factors after LR resection, were quite different from those of oLR.

Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.

PURPOSE: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. METHODS: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. RESULTS: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC. CONCLUSION: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.

A Case of Metaplastic Squamous Cell Carcinoma of the Breast that Showed a Pathological Complete Response After Neoadjuvant Chemotherapy with Weekly Paclitaxel.

BACKGROUND Primary squamous cell carcinoma of the breast is a rare type of metaplastic breast carcinoma, characterized by resistance to conventional chemotherapy agents. We report a case of metaplastic squamous cell carcinoma of the breast in which a pathological complete response was achieved after neoadjuvant chemotherapy with weekly paclitaxel and in which the patient remained disease free for 15 years and 7 months. CASE REPORT A 40-year-old woman had a palpable 5-cm-diameter tumor in the right breast that was diagnosed as metaplastic squamous cell carcinoma of the breast based on core needle biopsy. The patient was initially treated with an adjuvant chemotherapy (AC) regimen consisting of doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) as neoadjuvant chemotherapy. Because the tumor grew rapidly and the skin redness increased after 1 cycle of the AC regimen, 12 cycles of weekly paclitaxel 80 mg/m² were subsequently administered. The tumor responded dramatically to paclitaxel. The patient underwent mastectomy with level II axillary lymph node dissection. No residual tumor cells were found, which indicated pathological complete response. The patient is currently disease free at 15 years and 7 months after the operation. CONCLUSIONS To our knowledge, there are no previous reports of metaplastic squamous cell carcinoma of the breast in which pathological complete response was achieved by treatment with neoadjuvant chemotherapy with weekly paclitaxel (80 mg/m²).

A new indication and surgical procedure to reduce fat necrosis after breast-conserving surgery using an inframammary adipofascial flap.

BACKGROUND: There is little information on the risk factors for fat necrosis after breast-conserving surgery using an inframammary adipofascial flap (IAF). METHODS: We conducted a retrospective cohort study from a single institution evaluating the risk factors for fat necrosis after breast-conserving surgery using an IAF (n = 41) performed from 2005 to 2020 for newly diagnosed stage 0-2 breast cancer or phyllodes tumor. RESULTS: Age (≥50 years of age vs. <50 years of age), mammographic density (fatty vs. other) and operation period (before vs. after revision of surgical procedure and patient indication) were significantly associated with fat necrosis (p = 0.006, p = 0.04 and p = 0.02, respectively). CONCLUSION: Our study suggested that the use of an IAF with crescent dermis and selection of appropriate cases for IAF after breast-conserving surgery may be useful for the purpose of reducing fat necrosis. Further study is needed.