[Does Early Olaparib Administration Improve Prognosis in Patients with HER2-Negative Metastatic Breast Cancer and BRCA1 and/or BRCA2 Pathogenic Variants?-A Case Report].

We herein describe our experience with patients who had been diagnosed with BRCA1/2 pathogenic variants and metastatic breast cancer. Three patients who experienced postoperative recurrences had received chemotherapy before recurrence, while an additional patient with stage Ⅳ disease at diagnosis required chemotherapy before olaparib administration. Prior anthracycline and/or taxane-based therapies needed prior to administration of poly(adenosine diphosphate ribose) polymerase inhibitors might still be controversial in terms of patient benefits.

[Relationship between HER2 Gene Amplification and the Therapeutic Effect of Pertuzumab in HER2-Positive Breast Cancer].

OBJECTIVE: We examined the therapeutic effect of adding of pertuzumab in combination with trastuzumab as neoadjuvant chemotherapy for HER2-positive breast cancer. PARTICIPANTS: Overall, 27 patients with HER2-positive breast cancer who had completed neoadjuvant chemotherapy and undergone surgery between January 2014 and January 2020 were included in the study. We performed a retrospective analysis of the relationship between HER2 gene amplification and the therapeutic effect of pertuzumab in this group. For the anti-HER2 treatment, only trastuzumab was administered to all patients until December 2018, and then a combination of trastuzumab and pertuzumab was administered to 4 patients from January 2019. RESULTS: The case distribution based on histological therapeutic effect was: 4 patients with Grade 1, 12 patients with Grade 2, and 11 patients with Grade 3. Patients with immunohistochemistry scores of 3+ and high signal ratios of HER2/ CEP17 in FISH testing tended to have better therapeutic outcomes than other patients. DISCUSSION: Outcomes similar to those observed in this study were reported in other cases where pertuzumab was used for anti-HER2 treatment. We expected that the therapeutic effects of pertuzumab would be better in patients with high HER2 expression. However, further research is required to understand the effects of pertuzumab in patients with cT1c that were not included in the Neo Sphere trial. The therapeutic effects of adding pertuzumab to the treatment in patients with cT1c and lymph node-positive breast cancer were indicated by comparison with our cases.

Can digital breast tomosynthesis improve identification of malignant calcifications?

Digital breast tomosynthesis (DBT) is an emerging imaging tool for both the screening and diagnosis of breast cancers. However, the use of DBT in diagnosis of calcifications remains ambiguous. In this study, we investigated DBT findings that might help differentiate between benign and malignant calcifications. We enrolled 256 subjects and evaluated 303 breasts with grouped or segmental calcifications. All imaging examinations were performed using two-directional full-field digital mammography (FFDM) and DBT. We divided subjects into two groups, namely, "dense" and "fatty," based on the quantity of breast tissue and evaluated whether the growth of cancer causes increased the density overlapping with calcifications. Increased overlapping density was significantly associated with malignant calcifications (p < 0.001), and the identification of increased density was more accurate using DBT than using FFDM. Furthermore, we used DBT to evaluate whether segmental calcifications were continuous or discontinuous. Significantly more malignant than benign calcifications were associated with a continuous distribution (p = 0.035). Increased density overlapping with grouped calcifications was significantly associated with invasive cancers (p = 0.017). The findings of this study suggest that DBT improves the ability to differentiate between benign and malignant calcifications.

Pegfilgrastim-induced fatigue and leukocytosis improved following dose reduction in a young patient with breast cancer: A case report.

Dose-dense (DD) chemotherapy is a treatment option for patients with high-risk premenopausal breast cancer. Pegfilgrastim may be administered as prophylaxis against the development of febrile neutropenia and enables the continuation of the DD schedule; however, it is associated with adverse effects, including bone and muscle pain and fatigue. We herein describe our experience with pegfilgrastim administration alongside DD chemotherapy in a patient with breast cancer. A 29-year-old female patient was diagnosed with locally advanced breast cancer during lactation. The patient was diagnosed with cT2N1M0, stage IIB triple-negative breast cancer and underwent four cycles of DD chemotherapy with epirubicin plus cyclophosphamide, followed by four cycles of docetaxel (DTX) every 2 weeks preoperatively, with 3.6 mg pegfilgrastim administered subcutaneously on day 3 of each cycle. The absolute neutrophil count (ANC) was 2,700, 8,400, 11,100, 13,300 and 15,000/mm3 on day 1 of each cycle. The patient experienced fatigue after each pegfilgrastim injection and was considered to be a high responder to pegfilgrastim. Therefore, 1.8 mg pegfilgrastim on day 3 of the first DD-DTX cycle was recommended. On day 1 of the second cycle, the ANC was 13,090/mm3. The patient experienced less fatigue after the administration of 1.8 mg pegfilgrastim, but there was a significant decline in her performance status. As there is currently no evidence of pegfilgrastim dose reduction to below 1.8 mg, pegfilgrastim was omitted on day 3. On day 14, the patient developed viral enteritis, fever (38°C), and an ANC of 297/mm3. Therefore, the third cycle was postponed. After 1 week, the patient's ANC recovered to 2,480/mm3 and she was administered the third cycle with 3.6 mg pegfilgrastim on day 3. Between January 2015 and March 2018, a total of 55 patients with breast cancer received chemotherapy with pegfilgrastim at the Shiga General Hospital. No patients other than the one presented herein experienced leukocytosis during chemotherapy. Although this was a rare complication, a dose of 1.8 mg pegfilgrastim was effective in palliating the patient's symptoms and preventing DD chemotherapy discontinuation.

Correction to: Multidisciplinary treatment for locally advanced breast cancer with internal mammary lymph node metastasis in an elderly patient.

[This corrects the article DOI: 10.1007/s13691-018-0344-z.].

Effectiveness and safety of surgical glove compression therapy as a prophylactic method against nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy.

BACKGROUND: We have developed a surgical glove (SG)-compression therapy and reported that this method significantly reduced the overall occurrence of grade 2 or higher nanoparticle albumin-bound-paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) from 76.1% to 21.4%. In this multicenter single-arm confirmatory study, we investigated the efficacy and safety of SG-compression therapy for the prevention of nab-PTX-induced PN, compared with the incidence of grade 2 or higher PN in published literature as controls. PATIENTS AND METHODS: Primary breast cancer patients who received 260 mg/m2 of nab-PTX were eligible for this study. Patients wore two SGs (one size smaller than the tight-fitting size) in each hand for 90 min. PN was evaluated at each treatment cycle using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The temperature of each fingertip was measured using thermography. RESULTS: Between October 2016 and June 2017, 58 patients were evaluated. The incidence of CTCAE grade 2 or higher PN was as low as 13.8% following SG-compression therapy. A goodness-of-fit test proved that the overall incidence of 13.8% grade 2 or higher PN in this study was comparable to the hypothesis-predicted value (13%). No adverse events, including compression intolerance or skin disorders caused by use of SG, were observed. SG-compression therapy significantly reduced the temperature of each fingertip by 1.3°C-2.3 °C compared to pre-chemotherapy level. CONCLUSIONS: This study suggested the safety and efficacy of SG-compression therapy for the amelioration of CIPN. CLINICAL TRIAL NUMBER: UMIN 000024836.

Multidisciplinary treatment for locally advanced breast cancer with internal mammary lymph node metastasis in an elderly patient.

Internal mammary lymph node (IMLN) metastasis is one of the important prognostic indicators in breast cancer. However, the management for IMLN metastasis is not established. The dissection for IMLN metastasis is not recommended in the National Comprehensive Cancer Network guidelines version3. 2015. Furthermore, radiotherapy including IMLN region and biopsy have attendant risks and hence should be performed with caution. Here, we describe our experience of multidisciplinary treatment for locally advanced breast cancer with IMLN metastasis in an elderly patient. Core-needle biopsy of the breast tumor histologically diagnosed the tumor as estrogen receptor positive, progesterone receptor positive, human epidermal growth factor receptor-2 negative, and high Ki-67 labeling index. IMLN swelling was detected by ultrasonography and breast cancer metastasis was diagnosed by fine-needle aspiration cytology. The patient underwent mastectomy and axillary lymph node dissection, followed by postmastectomy radiation therapy. Systemic therapy using tegafur plus uracil (UFT®; Taiho Pharmaceutical Co., Ltd, Tokyo, Japan) and letrozole was beneficial treatment for disease control.

Prevention of locoregional recurrence and distant metastasis in Japanese breast cancer patients using Japanese standard postoperative radiation fields: Experience at a single institution.

BACKGROUND: Radiotherapy is an effective local control therapy for breast cancer. Locoregional control is associated with distant metastasis risk and survival after surgery. AIM: We aimed to evaluate whether Japanese standard postoperative radiotherapy after surgery correlates with disease-free survival (DFS) and overall survival and clarify the characteristics of patients who benefit from it. METHOD AND RESULTS: This retrospective study included 626 operable breast cancer patients. Tumor characteristics and survival outcomes were compared between patients who received radiotherapy and those who did not. Cox proportional hazard analysis was used to analyze prognostic factors for DFS and perform subgroup analysis. Propensity score matching was used to evaluate the efficacy of radiotherapy using a logistic regression model in patients who received radiotherapy or did not. The median follow-up duration after diagnosis of breast cancer was 63 months. DFS and overall survival were better in the irradiated group (P= .002 and P = .001, respectively). Radiotherapy was more effective for estrogen receptor (ER)-positive disease and for early breast cancer without lymph node metastasis. Multivariate analysis revealed that radiotherapy was a dependent risk factor for recurrence or metastasis. CONCLUSION: Radiotherapy prevents distant metastasis and recurrence in early breast cancer patients. In particular, ER-positive, node-negative patients benefit from Japanese standard tangent field radiation.

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

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.

Patients who achieved long-term clinical complete response and subsequently terminated multidisciplinary and anti-HER2 therapy for metastatic breast cancer: A case series.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) -positive breast cancers tend to be more aggressive and more likely to recur than HER2-negative breast cancers. However, novel anti-HER2 therapies have dramatically improved the prognosis of patients with HER2-positive breast cancer. CASE REPORT: We review the cases of 4 women with metastatic breast cancer who achieved clinical complete response (cCR) and terminated their systemic therapy. Two patients had de novo metastatic disease and two patients experienced relapse after adjuvant therapy. All patients achieved cCR using multidisciplinary therapy, experienced prolonged complete remission, and subsequently terminated their systemic therapy without experiencing secondary recurrence. CONCLUSION: There is no evidence that systemic therapy can be safely terminated after a specific time period, although adverse events (e.g., cardiotoxicity) and unnecessary treatment should be avoided. Thus, it is possible that select patients may be suitable for termination of systemic therapy after they have achieved a prolonged period of cCR.

Assisted reproductive technology is effective for but does not affect the prognosis of young patients with breast cancer: Experience in a single institution.

Assisted reproductive technology (ART) helps women preserve fertility after chemotherapy for cancer treatment. We examined the long-term survival of patients with early breast cancer who did or did not receive ART, as well as post-treatment pregnancy and childbirth rates. Our study consisted of 44 young patients (≤35 years of age). Eight patients were pregnant post-treatment; however, none of these patients received ART intervention. ART intervention prevented patient omits of necessary treatment to avoid adverse events. It did not affect the prognosis of patients with breast cancer. Technical improvements are needed to increase the likelihood of pregnancy after breast cancer treatment.

Low neutrophil-lymphocyte ratio correlates with extended survival in patients with metastatic breast cancer who achieved clinically complete response following multidisciplinary therapy: A retrospective study.

The prognosis of patients with metastatic or recurrent breast cancer (MBC) is improving as novel treatments are developed. The present study compared the clinical characteristics of patients with MBC with or without a complete clinical response (cCR) and identified the survival-associated factors. This was a retrospective study, which included 171 patients treated for MBC between 2011 and 2017 at the Shiga Medical Center for Adults. Neutrophil to lymphocytes ratios (NLRs) were determined in blood samples. The median follow-up period following diagnosis of MBC was 44 months (range, 0-217 months). A total of 32 patients (18.7%) achieved a cCR. Compared with the non-cCR group, the cCR group had significantly fewer metastases or recurrences (P<0.001), significantly fewer visceral metastases (P<0.001), a significantly lower NLR (P<0.001) and were diagnosed with primary breast cancer at a significantly earlier stage (P=0.003). Prognosis was significantly improved in the cCR group compared with the non-cCR group (P<0.001) and a high NLR (≥19) independently predicted worse survival in a multivariate analysis (P=0.0218; hazard ratio, 1.75; 95% confidence interval, 1.09-2.85). In conclusion, the present study determined that achieving a cCR and having a low NLR are important for the long-term survival of patients with MBC.

Overall survival of elderly patients with breast cancer is not related to breast-cancer specific survival: A single institution experience in Japan.

BACKGROUND: As the aging population grows, the number of elderly breast cancer patients has rapidly increased especially in Japan; a suitable treatment for elderly patients, considering chronic comorbidities and treatment tolerance, is urgently needed. METHODS: In this retrospective study, 286 elderly breast cancer patients were investigated. Tumor characteristics and survival outcome were compared between 70-79-year-old and ≥ 80-year-old groups. Disease-free survival, overall survival, and breast cancer-specific survival were compared, and the effect of variables was analyzed statistically. For resectable cases, prognoses were compared based on treatment (standard therapy or undertreated). RESULTS: Tumor characteristics were similar between groups, but the Ki-67 labeling index tended to be higher in older patients. Elderly patients with resectable cancer tended to be undertreated. During the median 59-month follow-up period, overall survival was significantly worse in the ≥80-year-old than in the 70-79-year-old group (p < 0.001), but disease-free and breast cancer-specific survivals were equivalent. Recurrence or death event hazard rates tended to be lower in patients receiving standard treatment. CONCLUSIONS: Standard multidisciplinary treatment for breast cancer prevents recurrence and metastasis and tends to extend breast cancer-specific survival even in elderly patients.

The relationship between serum E2 levels and recurrence in premenopausal, ER-positive breast cancer patients: A retrospective study.

BACKGROUND: Among estrogens, estradiol (E2) has the strongest physiological activity as a stimulator in estrogen receptor (ER)-positive breast cancer. The aim of this study is to investigate E2 dynamics during endocrine therapy and to explore the optimal environment in which tamoxifen (TAM) exhibits better efficacy for ER-positive premenopausal early breast cancer patients. METHODS: This is a retrospective study enrolled 194 patients with premenopausal ER-positive early-stage breast cancer who aging ≤45 years at onset and receiving luteinizing hormone-releasing hormone-agonist (LHRH-a) and TAM-therapy. Approximately half of the patients also received pre- or post-operative chemotherapy as adjuvant systemic therapy. We studied the relationship between recurrence and serum hormonal dynamics during adjuvant therapy. We monitored the concentrations of E2 and, follicle-stimulating hormone (FSH) in the blood before, during, and after treatment. The median follow-up period was 80 (14-555) months. RESULTS: Forty-six (23.7%) patients developed recurrent breast cancer after surgery. The prognoses were favorable in the group receiving longer LHRH-a exposure if those patients did not receive chemotherapy as their adjuvant therapy. Paradoxically, patients with high serum E2 levels after LHRH-a showed a low recurrence ratio. This phenomenon might be explained by the similar mechanisms of estrogen therapy after estrogen depletion by aromatase inhibitor (AI) therapy for metastatic breast cancer. CONCLUSION: Among patients who received endocrine therapy without adjuvant chemotherapy, those with longer LHRH-a exposure had favorable prognoses. A potential association was observed between recurrence and E2 concentrations in women with premenopausal ER-positive early-stage breast cancer.

Palliative surgery for giant mucinous carcinoma of the breast in an elderly patient: A rare case report.

Mucinous breast carcinoma (MBC) is relatively rare, accounting for <10% of all breast cancers in women. These tumors are usually slow-growing and exhibit less aggressive characteristics compared with other types of breast cancer. Between 1989 and 2016, 55 patients underwent surgery for MBC at the Shiga Medical Center for Adults (Moriyama, Japan). The 10-year disease-free survival (DFS) and overall survival rates were 94.5 and 100.0%, respectively. Specifically, the 10-year DFS rates of pure MBC (PMBC) and mixed MBC were 97.7 and 83.3%, respectively. We herein report the case of a sizeable mucinous carcinoma causing rupture of the skin and bleeding due to tumor pressure. Palliative surgery was performed in order to remove the bleeding source after a total of 5 months of preoperative endocrine-based therapy. In conclusion, palliative surgery improved the patient's quality of life and may be a viable option for PMBC patients. The aim of the present study was to review the characteristics and management of these tumors, particularly in elderly patients.

A case of metaplastic breast cancer that showed a good response to platinum-based preoperative chemotherapy.

Patients with metaplastic breast cancer (MBC) exhibit reduced response to chemotherapy and have poor prognosis. We investigated a case of MBC that showed a positive response to preoperative chemotherapy, resulting in near pathological complete response (pCR). A 59-year-old woman complained of a lump in her right breast. Magnetic resonance imaging (MRI) showed the presence of a solid mass that was 24 mm in diameter. The pathological diagnosis was MBC with cartilaginous differentiation. The clinical stage was T2N0M0, stage IIA according to the International Union against Cancer (UICC) criteria. To observe the response to chemotherapy, we gave her preoperative chemotherapy. The patient was monitored closely, since we realized that failure of chemotherapy carries a risk of tumor progression. Evaluation was carried out using ultrasound, MRI, fluorodeoxyglucose (FDG) positron emission tomography (PET), and a Ki-67 labeling index after the first cycle of chemotherapy, and ultrasound after each additional cycle. FDG-PET showed a positive response after the first cycle of chemotherapy. The patient underwent 4 cycles of docetaxel (75 mg/m(2)) and cisplatin (75 mg/m(2)) followed by 4 cycles of cyclophosphamide (500 mg/m(2)), doxorubicin (50 mg/m(2)), and cisplatin (50 mg/m(2)). Ultrasound showed decreases in tumor size after each cycle of chemotherapy. After chemotherapy, MRI showed nearly complete regression of the tumor. Partial mastectomy was performed. Pathological examination showed few cancer cells remaining, indicating near pCR. We report a case of MBC that responded well to platinum-based preoperative chemotherapy. We propose that preoperative chemotherapy may be an option for treatment of MBC in conjunction with careful monitoring.

Spontaneous necrosis of solid gallbladder adenocarcinoma accompanied with pancreaticobiliary maljunction.

A 71-year-old Japanese man with acute cholecystitis and an incarcerated gallbladder (GB) stone was admitted. Plain ultrasonography (US) incidentally detected a mass-like lesion in the fundus. Doppler US revealed that this elevated lesion had no blood flow. Computed tomography showed a relatively low-density mass, measuring 5 cm multiply 4 cm in diameter, with no positive enhancement. Magnetic resonance imaging showed a mass in the fundus with a slightly low intensity on T1-weighted images and a slightly high intensity on T2-weighted images. We were agonized in making the qualitative diagnosis of mass-like lesions of the fundus, such as a benign tumor, cancer, or debris. We performed laparoscopic cholecystectomy, because the incarcerated GB stone clearly caused acute cholecystitis. Intra-operative cholangiography clearly revealed pancreaticobiliary maljunction. Amylase levels in the common bile duct and gallbladder were quite high. The elevated lesion in the fundus clearly showed severe necrosis. Although this necrotic nodule included non-viable adenocarcinoma cells, viable cancer cell nests were located in the muscularis propria and subcutaneous layer. Histopathological examination confirmed a solid adenocarcinoma. Thus, we diagnosed it as a gallbladder cancer, based on histopathological analysis of the resected specimen. We therefore undertook radical surgery, including wedge resection of the liver, radical dissection of regional lymph nodes, and resection of the extrahepatic bile duct. Histopathological findings revealed no cancer, hyperplasia or dysplasia in the additionally resected specimens. The patient was finally staged as T2, N0, H0, P0, M(-), stage II. We present the first case of spontaneous necrosis of solid gallbladder adenocarcinoma, with a review of previous studies.