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.

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.

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.

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.

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.

[Bi-weekly nab-paclitaxel and trastuzumab therapy effective against recurrent breast cancer with multiple lung metastases in elderly patient who had previously undergone two chemotherapeutic regimens for treatment of metastatic disease-a case Report].

We herein report a 75-year-old patient with recurrent hormone-nonresponsive, HER2-positive breast cancer who presented with multiple lung metastases. She had undergone a mastectomy followed by adjuvant chemotherapy with FEC, CMF, and UFT. Forty-six months after the surgery, multiple lung, liver, and bone metastases were observed. Docetaxel and trastuzumab were administered as first-line chemotherapy for 13 months. A partial response and stable disease were observed, but progressive disease in the lung and brain was subsequently revealed. The patient then underwent g-knife treatment for brain metastasis. Lapatinib and capecitabine treatment was administered as second-line chemotherapy for 9 months. Stable disease was observed, but progressive disease in the lung metastases with clinical symptoms including cough, exertional dyspnea, and general malaise was revealed. As third-line chemotherapy, the patient was administered low-dose, bi-weekly nab-paclitaxel(150mg/m2)and trastuzumab therapy. Four weeks after beginning the nab-paclitaxel and trastuzumab treatment, the cough disappeared; 2 months after beginning the therapy, a partialresponse in the lung metastases was seen. The patient is well and the treatment has been continued for 50 weeks. No progression has been seen. Bi-weekly nab-paclitaxel treatment appears to have few side effects and might be an effective treatment option for patients with recurrent breast cancer.

[Nineteen years postoperatively, anastrozole, UFT and cyclophosphamide combination therapy remained effective against recurrent hormone responsive breast cancer with intraabdominal lymphnode, pleural, skin and bone metastases in old age following sixteen-year tamoxifen treatment - a case report].

We report an 89-year-old patient with recurrent hormone-responsive breast cancer who presented with pleural, skin and bone metastases. Nineteen years previously, she had undergone a mastectomy and then for 16 years received adjuvant hormone therapy. The patient was orally administered a combination therapy of anastrozole, UFT and cyclophosphamide. A remarkable response was seen after 5 months, and no side effects were observed. The patient became well and the treatment was continued without relapse at 8 months. Oral anti-cancer treatments in combination with hormone therapy appear to have few side effects and might be an effective treatment option for recurrent breast cancer patients.

Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results.

BACKGROUND: Aromatase inhibitors (AI) have been established as the gold-standard therapy for postmenopausal patients. Worldwide, adjuvant denosumab at a dose of 60 mg twice per year reduces the risk of clinical fractures in postmenopausal patients with breast cancer who received AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss had not been prospectively evaluated in Japan. Previously, we reported the 12-month effect of denosumab in Japanese patients for the first time; the primary endpoint was the change in the percentage of bone mineral density (BMD) of the lumbar spine from baseline to 12 months. METHODS: This secondary follow-up study prospectively evaluated the change in the percentage of BMD of the lumbar spine from baseline to 24 months. Postmenopausal women with early-stage, histologically confirmed, hormone receptor-positive, invasive breast cancer who were receiving or scheduled to receive AI were included. Denosumab was administered subcutaneously on day 1 of the study and then 6, 12, 18, and 24 months. The lumbar spine and bilateral femoral neck BMD was measured at baseline and 6, 12, 18, and 24 months. RESULTS: At 18 and 24 months, the lumbar spine BMD increased by 5.9 and 7.0%, respectively. The femoral neck BMD also increased. Grade ≥ 2 hypocalcemia, osteonecrosis of the jaw, and atypical femoral fractures did not occur. CONCLUSIONS: Our prospective study showed that semiannual treatment with denosumab was associated with continuously increased BMD in Japanese women receiving adjuvant AI therapy for up to 24 months, regardless of prior AI treatment.

Efficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer.

BACKGROUND: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD. PATIENTS AND METHODS: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I-IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1-L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were ETHICS AND DISSEMINATION:: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.

[Doxifluridine, medroxyprogesterone acetate and cyclophosphamide (DMpC) combination therapy is effective against recurrent triple negative breast cancer--a case report].

We report a postmenopausal recurrent breast cancer patient with triple negative disease who presented with right recurrent nerve palsy. Nine years previously, she had undergone a mastectomy. FDG-PET scan revealed neck lymph node metastases from the breast cancer. The recurrent nerve palsy was thus considered to have been caused by the lymph node metastases. The patient was orally administered DMpC (doxifluridine, medroxyprogesterone acetate and cyclophosphamide) combination therapy. This resulted in a remarkable response after five months, with the recurrent nerve palsy completely disappearing at six months. No side effects from the treatment were observed. The patient was well and the treatment was being continued without relapse at nine months. Oral anti-cancer treatments such as DMpC appear to have few side effects and might be an effective treatment option for recurrent breast cancer patients with triple negative disease.

[Therapeutic agents for disorders of bone and calcium metabolism: Zoledronic acid].

Intervenous (IV) bisphosphonates are used for cancer patients with hypercalcemia of malignancy (HCM) and breast cancer bone metastases (BM). Recently, zoledronic acid, the most potent third generation bisphosphonate, has been approved for both HCM and BM of broad tumors. It showed 850-fold stronger activity than pamidronate in bone resorption assay, and clinical efficacy against multiple cancer bone lesion has been confirmed in randomized clinical trials. Zoledronic acid becomes one of the most used bisphosphonate for cancer patients in the world, and the results of clinical trials for cancer treatment-induced bone loss or postmenopausal osteoporosis are now updating.

Erratum to immediate breast volume replacement using a free dermal fat graft after breast cancer surgery: multi-institutional joint research of short-term outcomes in 262 Japanese patients.

[This corrects the article on p. 179 in vol. 4, PMID: 26005649.].

Immediate breast volume replacement using a free dermal fat graft after breast cancer surgery: multi-institutional joint research of short-term outcomes in 262 Japanese patients.

BACKGROUND: Immediate volume replacement using a free dermal fat graft (FDFG) has been proven safe with early postoperative benefits. The aims of the present study were to clarify adequate indications and risk factors associated with operative morbidity. PATIENTS AND METHODS: A multi-institutional analysis of partial mastectomy with immediate volume replacement with FDFG was undertaken in 14 hospitals specializing in breast cancer treatment. Clinical and oncological variables were analyzed to identify factors associated with postoperative complications. RESULTS: A total of 262 cases were analyzed. Considering the observation period and overlap of patients, 13 (5.4%) out of 242 patients had complications within 1 month of surgery while 7 (4.6%) out of 151 patients developed complications 1-12 months after surgery. Two hundred and eleven out of 242 patients were statistically examined using a multivariate analysis, which revealed that the weight of resected breast tissue, size of implanted FDFG (cranio-caudal length), and weight of implanted FDFG were associated with a higher likelihood of postoperative complications. CONCLUSIONS: Immediate breast volume replacement using a FDFG after breast cancer surgery should be done for selected patients with breast cancer to avoid postoperative complications. The prospective and larger investigations are warranted for the establishment of appropriate guidelines.

A case of serum CEA disappearance curve after resection of breast carcinoma.

Carcinoembryonic antigen (CEA) elimination kinetics after tumor resection were measured in a case of breast cancer. A 45-year-old woman with a left breast carcinoma underwent surgery after neoadjuvant chemotherapy. The serum CEA level before surgery was 34.3 ng/ml. After sequential monitoring of serum CEA levels, postoperative serum CEA elimination kinetics were calculated using non-linear least square analysis with the fitting equation C(t)=(C0-Cp)exp(-kt)+Cp, where C(t) was the postoperative CEA level, t was the number days after surgery, C0 was the CEA level at postoperative time zero, Cp was the CEA at plateau, and k was the rate constant of elimination. Cp was calculated as 6.9 ng/ml, which was above the cut-off level and indicated residual malignancy. After adjuvant chemotherapy, CEA normalized to 1.8 ng/ml. In breast cancer patients with high preoperative serum CEA levels, our analytical method for CEA elimination might be useful for the detection of residual malignancies.

A case of granulomatous mastitis mimicking breast carcinoma.

A 58-year-old woman presenting with idiopathic granulomatous mastitis mimicking breast carcinoma is described. The mass was elastic, hard and painless, and located in the upper outer quadrant of the right breast. Fine needle aspiration cytology did not provide any diagnostic information. Mammography, ultrasonography and magnetic resonance imaging (MRI) strongly suggested malignancy. Excisional biopsy was performed for definitive diagnosis, and idiopathic granulomatous mastitis was demonstrated histopathologically. Neither wound complication nor recurrence has been identified in the patient, although corticosteroids were not used post operatively. We reviewed the literature, and found that our present case is rare in older patients, and that mammography, ultrasonography and MRI provide little information for differentiating between granulomatous mastitis and carcinoma.

Long-term survival after hepatectomy for large metastatic breast cancer: a case report.

Long-term survival after the resection for liver metastasis from breast cancer is rare. We report on a 49-year-old woman who has been alive and well for 12 years following hepatic resection for metastatic breast cancer. Fourteen years before, the patient underwent a radical mastectomy for cancer of the right breast. One year after the operation the patient presented with right upper quadrant pain and a large isolated right lobe liver metastasis was found. Initially, it was too large to be treated by hepatectomy. Thus, intra-arterial one-shot injection of 20 mg of mitomycin C mixed with 4 mL of lipiodol was given three times at 1-month intervals and was followed by 5-fluorouracil (250 mg) and mitomycin C (2 mg) administered 9 times at 2-week intervals through the implanted port. Additionally, 150 mg of 5-fluorouracil and 1200 mg of medroxiprogesterone acetate were orally administered for 5 months. These therapies led to a remarkable reduction in tumor size and the metastasis was safely resected by an extended right hepatic lobectomy. The specimen was completely necrotic and histologically no viable tumor cell was observed. In the present case, the aggressive preoperative chemo- and hormonal therapies might be significant in making a contribution to longer survival.

Combined large cell neuroendocrine carcinoma.

We report a case of combined large cell neuroendocrine carcinoma. A 78-year-old man with vertigo was referred to our hospital where chest X-ray revealed a tumor shadow in the right lung. A transbronchial lung biopsy specimen verified a diagnosis of non-small cell lung carcinoma (cT1N0M0). Right lower lobectomy with mediastinal lymph node dissection (#7, 8, 9) was performed. A postoperative histological diagnosis was combined large cell neuroendocrine carcinoma of a component of squamous cell carcinoma [pT4 (pm) N2M0]. The patient received concurrent chemoradiotherapy due to upper mediastinal lymph node metastasis 4 months after surgery. The chemoradiotherapy well responded and the patient remains well 9 months after surgery.

Intrapleural administration of a large amount of diluted fibrin glue for intractable pneumothorax. A clinical study based on 57 cases: including 2 unsuccessful cases.

OBJECTIVE: Pleurodesis using chemical agents has been applied to high-risk patients with pneumothorax. This treatment, however, is sometimes unsuccessful in patients with intractable pneumothorax. We have developed intrapleural administration of diluted fibrin glue as an effective treatment for such patients. METHODS: Fibrin glue was diluted 4-fold with saline and/or contrast media. Pleurodesis with a large amount of the diluted fibrin glue was performed in 55 high risk patients (57 cases, bil.2 patients) with intractable pneumothorax. RESULTS: The air leaks were stopped by administration of the glue in all except 2 patients. During the follow-up period, a recurrence rate of 10.5% was observed. These recurrent pneumothoraces were successfully treated using the same procedure with no further recurrence. Pyrexia (12.3%) and chest discomfort (8.8%) were observed as side effects, and there was no occurrence of severe chest pain or thoracic empyema. CONCLUSIONS: These results suggested that intrapleural administration of a large amount of diluted fibrin glue was an effective treatment for intractable pneumothoraces in high-risk patients.

[Weekly administration of gemcitabine in outpatient clinic for non-small cell lung cancer].

We treated inoperable or recurrent non-small cell lung cancer (NSCLC) patients with weekly outpatient administration of gemcitabine. The aim of this therapy was to improve or to maintain the patients' performance status. From November 1999 to December 2001, 15 NSCLC patients were treated with gemcitabine. The patients were 12 males and 3 females, 14 with adenocarcinoma and 1 with squamous cell carcinoma, aged 57 to 81 years old. A dose of 1,000 mg/m2 of gemcitabine was administered on days 1 and 8 every 3 weeks. Patients were treated for 1 to 17 (median 3) months. Performance status was maintained in 12 of 15 patients during this treatment. Average tumor marker doubling time was 289 days. Median survival time was 8.1 months. Weekly administration of gemcitabine in an outpatient setting is a useful treatment for inoperable or recurrent non-small cell lung cancer.

[Advanced breast cancer with lung and pleural metastases responsive to anastrozole--a case report].

A 63-year-old postmenopausal woman was referred to our hospital for treatment of ER positive advanced breast cancer. The patient had lung and pleural metastases with pleural effusion from breast cancer. She was treated with anastrozole, a 3rd-generation aromatase inhibitor, which brought about a marked regression of the lung tumor, and disappearance of pleural effusion. The patient experienced no adverse effects with this therapy. Anastrozole therapy is a useful treatment for postmenopausal women with ER positive advanced breast cancer.