Risk reduction of distant metastasis in hormone-sensitive postmenopausal breast cancer

Adjuvant endocrine therapy remains the principle strategy to reduce recurrence risk in postmenopausal women with early breast cancer. Studies of the natural history of breast cancer have shown that, while not reaching zero at any time point, the risk of recurrence is highest in the first 5 years following initial diagnosis and treatment. Within this initial 5 years, there is a peak of recurrence at the 2- to 3-year mark. Among the types of breast cancer recurrences observed at this early peak, distant metastasis (DM) predominates over local or contralateral relapse. DM recurrences are most strongly linked to breast-cancer-related death, and it has been suggested that adjuvant endocrine therapies that are most effective in minimizing the early peak of DM recurrence may have the most favorable impact on survival in women with early breast cancer. Aromatase inhibitors (AIs) including anastrozole, letrozole, and exemestane have gained popularity in the past few years as alternatives to 5 years of adjuvant tamoxifen, the previous standard of care. However, clinicians have not yet resolved how best to integrate AIs into breast cancer treatment; both upfront therapy (i.e., in lieu of tamoxifen) and a sequential/switch strategy (i.e., after some period of prior tamoxifen) have been proposed. The benefits and drawbacks of these approaches to AI treatment, particularly with respect to reducing early DM recurrences, are reviewed

Prognostic factors for survival after first recurrence in breast cancer: a retrospective analysis of 252 recurrent cases at a single institution.

[Introduction]Previous studies have shown that primary breast cancer patients with estrogen receptor (ER)-positive status have better outcomes in terms of both overall survival and disease-free intervals (DFI). However, 25.2 % of our ER-positive patients experienced recurrence. This study aimed to define factors potentially predicting survival after first recurrence in surgically treated patients with stage I–III breast cancer. [Methods]We retrospectively analyzed 252 females with recurrent breast cancer who had undergone surgery and been followed at Kyoto University Hospital in Japan. Age, clinical stage, pathological stage, axillary lymph node involvement, ER status at the time of diagnosis, progesterone receptor status, human epidermal growth factor receptor 2 status, operative method, adjuvant chemotherapy, adjuvant endocrine therapy, use of trastuzumab after recurrence, site of recurrence, DFI, and time of recurrence were examined for possible influences on survival after the first recurrence. [Results]Positive ER status and positive PR status at the time of diagnosis were significantly favorable factors of survival after first recurrence for patients with recurrence, p < 0.001 and p = 0.021, respectively. More than two sites of recurrence (p < 0.001) were associated with shorter survival time after the first recurrence on multivariate analysis. Survival of patients with recurrent breast cancer steadily improved from 1980–1994 to 1995–2008, significantly in ER-negative subgroups. [Conclusions]Positive ER status at the time of diagnosis is a powerful predictor for favorable survival after first recurrence. Survival time after first recurrence of breast cancer has steadily increased in recent decades. Advances in treatments and attitudes about breast cancer have contributed to this improvement in survival after first recurrence

Fatigue behavior and crack initiation of CAD/CAM resin composite molar crowns

Objective: The aim of this study was to evaluate long-term fatigue behavior using an in vitro step-stress accelerated life test (SSALT), and to determine the crack initiation point using in silico finite element analysis for computer-aided designed and manufactured (CAD/CAM) molar crowns fabricated from three commercial CAD/CAM resin composite blocks: Cerasmart (CS; GC, Tokyo, Japan), Katana Avencia Block (KA; Kuraray Noritake Dental, Niigata, Japan), and Shofu Block HC (HC; Shofu, Kyoto, Japan). Methods: Fifty-one mandibular first molar crowns luted on a resin core die were embedded in acrylic resin and covered with a polyvinyl chloride tube. Single compressive tests were performed for five crowns. SSALT was conducted for 36 crowns using three profiles and reliabilities at 120,000 cycles, and a Weibull analysis was conducted. The maximum principal strain of each CAD/CAM resin composite crown model was analyzed by three-dimensional finite element analysis. Results: Fracture loads of CS and KA (3784 ± 144 N and 3915 ± 313 N) were significantly greater than that of HC (2767 ± 227 N) (p < 0.05). Fracture probabilities at 120,000 cycles were 24.6% (CS), 13.7% (KA), and 14.0% (HC). Maximum principal strain was observed around the mesiolingual cusps of CS and KA and the distobuccal cusp of HC. Significance: CAD/CAM resin composite molar crowns containing nano-fillers with a higher fraction of resin matrix exhibited higher fracture loads and greater longevity, suggesting that these crowns could be used as an alternative to ceramic crowns in terms of fatigue behavior.Yamaguchi S., Kani R., Kawakami K., et al. Fatigue behavior and crack initiation of CAD/CAM resin composite molar crowns. Dental Materials 34, 1578 (2018); https://doi.org/10.1016/j.dental.2018.07.002

Phase Ib/II study of nivolumab combined with palliative radiation therapy for bone metastasis in patients with HER2-negative metastatic breast cancer

Radiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4–29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23–58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1–6.1 months) and 2.0 months (95% CI 1.2–3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted

ヒト シボウ ソシキ ユライ カンサイボウ ニ ユウドウサレル シボウ ソシキ サイセイ

京都大学0048新制・課程博士博士(医学)甲第14900号医博第3385号新制||医||977(附属図書館)27338UT51-2009-M814京都大学大学院医学研究科外科系専攻(主査)教授 長澤 丘司, 教授 戸口田 淳也, 教授 中尾 一和学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Pros and cons of immediate Vicryl mesh insertion after lumpectomy

Summary: Background: Lumpectomy is a standard surgery for breast cancer; however, it results in breast deformity, especially after radiation therapy. Wider surgical margin correlates lower local recurrence rate. However, bigger defect brings worse cosmetic outcome. The use of a simple filler for the defect is expected. We aimed to improve the cosmetic outcome by using an absorbable Vicryl mesh for breast reconstruction immediately post-lumpectomy. Methods: One sheet of Vicryl woven mesh was prepared for insertion, washed the cavity with natural saline, and placed into the space. The cosmetic outcome was scored for the size, shape, scar, and softness of the breast. The size, shape, color, and position of the nipple–areola complex were also scored. Adverse events were collected retrospectively. Results: From April 2008 to October 2014, 24 female patients received immediate Vicryl mesh insertion. A lumpectomy only group was recruited for cosmetic analysis. All patients received postsurgical radiotherapy. The mean cosmetic assessment score was 8.0 and 9.1 of 12 for the Vicryl mesh group and lumpectomy only group, respectively (P = 0.17). Sixteen patients had adverse events such as erythema at approximately 2 weeks post-surgery. No significant differences were shown except adverse events between two groups. No patient has had local recurrence thus far. Conclusion: Immediate Vicryl mesh insertion leads to significantly increased incidence of postoperative complications and delay in commencement of adjuvant radiotherapy. Furthermore, the cosmetic outcomes are not superior to that of no reconstruction. The development of superior biomaterials is anticipated for breast reconstruction after lumpectomy. Keywords: Breast cancer, Cosmetic outcome, Immediate Vicryl mesh insertion, Lumpectomy, Ultrasonograph

Orally administered S-1 suppresses circulating endothelial cell counts in metastatic breast cancer patients.

[Background]S-1 is an oral cytotoxic preparation that contains tegafur. Gamma-butyrolactone (GBL) is a metabolite of tegafur that is known to suppress vascular endothelial growth factor (VEGF)-mediated angiogenic activity. The aim of this study was to determine the change in circulating endothelial cell (CEC) counts, GBL levels, and angiogenesis-related factors during S-1 administration in metastatic breast cancer (MBC) patients. [Methods]Patients with HER2-negative MBC were eligible. S-1 was administered orally twice daily in a 4 week on/2 week off cycle until disease progression or unacceptable toxicity occurred. Blood was collected on the following: days 1, 43, 85 (before each cycle of S-1 administration), days 15, 57 (1 h after S-1 administration), and day 29. The CellSearch® system was used to count the CECs. The gas chromatographic–mass spectrometric method was used to measure plasma GBL and 5-FU levels. Levels of VEGF were assayed by enzyme-linked immunosorbent assay. [Results]A total of 18 patients were enrolled. The plasma GBL levels on days 15 and 57 were 41.3 ± 15.8 and 41.0 ± 11.2 ng/mL, respectively. The CEC levels decreased on day 15, and significantly low levels were maintained until day 85 (P = 0.002 vs day 1). The plasma VEGF levels significantly decreased on day 15 (P = 0.012 vs day 1) and had a tendency to decrease until day 57. [Conclusions]This exploratory study showed that GBL levels increased, VEGF levels decreased, and CEC levels were suppressed during S-1 administration. S-1 appears to have anti-angiogenic activity

Hormone signaling via androgen receptor affects breast cancer and prostate cancer in a male patient: A case report

Abstract Background Male breast cancer (MBC) is rare, accounting for only around 1% of all breast cancers. Most MBCs are hormone-driven. Not only the estrogen receptor (ER), but also other steroid hormone receptors, including the androgen receptor (AR) and progesterone receptor (PgR) are expressed in MBC. AR activation in breast cancer cells facilitates downstream gene expression that drives tumorigenesis in a similar manner to ER. AR-mediated signalling works paradoxically in breast cancer and prostate cancer, and cancer cells expressing the AR are endocrine-sensitive. Case presentation We describe a case of double cancer of MBC and prostate cancer. A 69-year-old man was referred to our hospital with a lump in his left breast in the 1990s. The patient had cT3N3M0, stage IIIC breast cancer, and underwent a mastectomy and axillary lymph node dissection. Though adjuvant chemotherapy was administered, he experienced pleural metastasis 2 months after the surgery. Two years after the recurrence during endocrine therapy with oral 5-fluorouracil, he complained of frequent urination. Radiological and histological examinations revealed that the patient had cT3N0M0, stage III primary prostate cancer with a prostate-specific antigen (PSA) level of 40.5 ng/mL. Germline mutations in the BRCA1 and BRCA2 genes were not tested. He received multidisciplinary, continuous therapy for both breast and prostate cancer; however, 5 and 3 years after each diagnosis, respectively, he experienced a deep vein thrombosis in his right leg related to the endocrine therapy. Liver metastasis progressed after he stopped breast cancer therapy. However, long-term disease control had been achieved with anti-estrogen therapy for breast cancer and estrogen replacement therapy for prostate cancer. Conclusions Several studies have shown that estrogen exposure after estrogen depletion likely causes apoptosis of ER-positive breast cancer cells. Our findings indicate that this also applies to the environment in male body. AR dominant signaling prevents breast cancer recurrence and metastasis, especially in MBC patients