Clinicopathological features, genetic alterations, and BRCA1 promoter methylation in Japanese male patients with breast cancer.

PURPOSE: Male breast cancer (MBC) is a rare cancer accounting for only 1% of all male cancers and is, therefore, poorly studied. We aimed to characterize the subtypes of MBC in Japanese patients based on genetic profiling, the presence of tumor-infiltrating cells, and the expression of immunohistochemical markers. METHODS: This retrospective study included 103 patients with MBC diagnosed between January 2009 and December 2019 at various hospitals in Japan. Clinicopathological patient characteristics were obtained from medical records, and formalin-fixed paraffin-embedded tissue specimens were analyzed for histological markers, mutations of 126 genes, BRCA1 methylation, and stromal tumor-infiltrating lymphocytes. RESULTS: The median patient age was 71 (range 31-92) years. T1-stage tumors were the most frequent (47.6%), and most were node negative (77.7%). The majority of tumors were positive for estrogen receptor (98.1%), progesterone receptor (95.1%), and androgen receptor (96.1%), and BRCA2 was the most frequently mutated gene (12.6%). The most common treatment was surgery (99.0%), either total mastectomy (91.1%) or partial mastectomy (7.0%). Survival analysis showed a 5-year recurrence-free survival rate of 64.4% (95% confidence interval [CI] 46.7-88.8) and a 5-year overall survival rate of 54.3% (95% CI 24.1-100.0). CONCLUSION: Japanese MBC is characterized by a high rate of hormonal receptor positivity and BRCA2 somatic mutation. Due to the observed clinicopathological differences in MBC between the Western countries and Japan, further prospective studies are needed to evaluate the most suitable treatment strategies.

[Experience of Fulvestrant for Hormone Receptor-Positive HER2-Negative Advanced and Metastatic Breast Cancer].

Several cases of hormone receptor-positive HER2-negative advanced and recurrent breast cancer treated with fulvestrant (FUL)were retrospectively investigated to assess the efficacy and safety of the treatment. FUL was administered to a total of 41 patients-33 with recurrent and 8 with Stage IV cancer-from January 2012 to September 2016. The median number of lines that used FUL was 3, the median time to treatment failure(TTF)was 7 months, the overall response rate(RR)was 19.5%, and the clinical benefit rate(CBR)was 53.6%. Our result was similar to those of the FIRST and the FALCON studies, which showed a decrease in RR after the fourth-line. With regard to RR, FUL seemed to provide better results at Cthird-lines of treatment. While a shorter TTF was seen in the cases with liver metastases, a longer TTF was seen in the cases with soft tissue metastases. Therefore, it may be helpful to consider the site of metastasis when predicting the effects of FUL.

[Efficacy of Palliative Radiotherapy for Unresectable Advanced Gastric Cancer with Bleeding].

Bleeding and obstruction negativelyimpact qualityof life for patients with unresectable advanced gastric cancer. There are several choices against bleeding and obstruction such as surgery, endoscopic therapy, radiotherapy and interventional radiology. We report on an 85-year-old woman with StageIV gastric cancer with tumor bleeding. Radiation therapyof 30 Gyin 10 fractions was performed. Anyadverse events were not confirmed. Bleeding or obstruction did not occur for 7 months after radiation therapy. Palliative radiation therapy to gastric cancer can be a reasonable option for patients with unsuitable general conditions for surgical intervention.

[A Case of Gemcitabine and Nab-Paclitaxel Therapy for Multiple Metastatic Pancreatic Cancer].

Pancreatic cancer is one of the leading causes of cancer-related death in Japan. Nab-paclitaxel(nab-PTX)and gemcitabine( GEM)combination chemotherapysignificantlyimproved overall survival in a phase III trial(MPACT). This combination chemotherapyhas become one of the first-line treatments for patients with metastatic pancreatic cancer since December 2014. We report a case of a patient who underwent this chemotherapyfor recurrence of pancreatic head cancer. A 64-yearold man, who underwent curative resection of pancreatic cancer 2 years ago, relapsed with multiple lung metastases and a para-aortic nodal metastasis. The patient was treated with combination chemotherapyof nab-PTX 125mg/m2 plus GEM 1,000mg/m2. He died from carcinomatous pleurisy1 9 months after starting the chemotherapy. The patient skipped scheduled chemotherapyonly3 times due to Grade 3 neutropenia during his clinical course over 19 months. The combination regimen of nab-paclitaxel and gemcitabine is thought to be a well-tolerated and standard treatment for metastatic pancreatic cancer.

Case Report of Complete Response to Olaparib in a Patient with Breast Cancer Brain Metastases.

Introduction: Breast cancer is the second most common cause of central nervous system (CNS) metastases. It has been shown that the median time from breast cancer diagnosis to CNS metastasis is 30.9 months and that the overall median survival after metastasis is extremely poor at 6.8 months. Although treatment options for ErbB2 Receptor Tyrosine Kinase 2 (ERBB2)-positive breast cancer brain metastasis (BCBM) have been reported, effective treatment options for ERBB2-negative BCBM, which has one of the worst prognoses, are limited. Olaparib is one of the standard treatments for germline BRCA1/2 mutated (gBRCA1/2mt), ERBB2-negative, metastatic, or recurrent breast cancer. However, there is minimal existing evidence to evaluate the efficacy of olaparib in BCBM. Case Presentation: In our report, we assessed the case of a Japanese woman in her early 30s, ERBB2-negative, gBRAC2mt-positive BCBM, who achieved a complete response and prolonged progression-free survival of 9 months after the initiation of treatment with olaparib. Conclusions: Thus, our case report demonstrated the significant efficacy of olaparib in BCBM treatment. Furthermore, we highlighted the need for more studies to investigate the efficacy of olaparib and explore the efficacy of poly ADP ribose polymerase inhibitors in BCBM.

The Impact of Being Underweight on the Prognosis of Older Patients With Early Breast Cancer.

Background/Aim: The number of older patients with breast cancer has been increasing and a major challenge is to develop optimal treatment strategies for these patients, who often have comorbidities. Obesity is reportedly a poor prognostic factor in breast cancer, however there is limited research on underweight patients. Clarifying the relationship between physique and prognosis may contribute to the establishment of optimal treatment strategies for older patients with breast cancer. Patients and Methods: This retrospective study examined clinicopathological data from a multicenter collaborative database on 1,076 patients aged 70 years or older who had undergone curative surgery. According to the body mass index (BMI), patient physique was defined as underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2) or obese (≥25 kg/m2). In this study, we explored the relationship between the physique of patients with breast cancer and outcomes. Results: Underweight patients had a significantly lower rate of chemotherapy administration (p=0.017) and a higher rate of presence of other cancer (p=0.022). During the observation period (median of 75.2 months), 133 patients (12%) developed recurrent disease and 131 patients (12%) died. Age, BMI, tumor size, progesterone receptor and the presence of other cancer were independent factors relating to overall survival (p<0.001, p=0.027, p=0.002, p=0.008 and p=0.005, respectively). Patients with a low BMI had a significantly shorter overall survival, but there was no association with disease-free survival in this subset of patients. Conclusion: Overall survival was shorter in underweight older patients with breast cancer. Our data indicate that being underweight should be considered both in treatment decisions and in future studies of outcomes for older patients with breast cancer.

Response to lenvatinib and pembrolizumab combination therapy in pembrolizumab-pretreated relapsed endometrial cancer.

Uterine endometrial cancer is one of the most common gynecological malignancies worldwide. With relatively few options for late-line therapies for advanced or relapsed endometrial cancer, the use of pretreated therapies may broaden the choice of treatments. Here, we report a case of recurrent microsatellite instability-high endometrial cancer that acquired resistance to pembrolizumab but favorably responded to the lenvatinib and pembrolizumab combination therapy. Lenvatinib combined with pembrolizumab may be effective against endometrial cancer resistant to pembrolizumab monotherapy, encouraging its use regardless of prior administration of immune checkpoint inhibitors. Further investigation on the lenvatinib and pembrolizumab combination therapy and the mechanism underlying its anticancer effect may provide new insights into cancer immunotherapy and tumor microenvironments.

Is adjuvant chemotherapy necessary in older patients with breast cancer?

BACKGROUND: Due to the lack of clinical trials on the efficacy of chemotherapy in older patients, an optimal treatment strategy has not been developed. We investigated whether adjuvant chemotherapy could improve the survival of older patients with breast cancer in Japan. METHODS: We retrospectively analyzed data of patients with breast cancer aged ≥ 70 years who underwent breast cancer surgery in eight hospitals between 2008 and 2013. Clinical treatment and follow-up data were obtained from the patients' medical electric records. RESULTS: A total of 1095 patients were enrolled, of which 905 were included in the initial non-matched analysis. The median age and follow-up period were 75 (range 70-93) and 6.3 years, respectively. Of these patients, 127 (14%) received adjuvant chemotherapy (Chemo group) while the remaining 778 (86%) did not (Control group). The Chemo group was younger (mean age in years 73 vs 76; P < 0.0001), had a larger pathological tumor size (mean mm 25.9 vs 19.9; P < 0.0001), and more metastatic axillary lymph nodes (mean numbers 2.7 vs 0.7; P < 0.0001) than the Control group. The disease-free survival (DFS) and overall survival (OS) did not differ significantly between the two groups (P = 0.783 and P = 0.558). After matched analyses, DFS was found to be significantly prolonged with adjuvant chemotherapy (P = 0.037); however, OS difference in the matched cohort was not statistically significant (P = 0.333). CONCLUSION: The results showed that adjuvant chemotherapy was associated with a reduced risk of recurrence, but survival benefits were limited.

Breast Cancer Treatment in a Patient with Decubitus Ulcer Infection Secondary to Spina Bifida: Surgical Resection versus Neoadjuvant Chemotherapy.

Spina bifida (SB) is a congenital neural tube defect that often presents with neurological disability and decubitus ulcers. A 66-year-old woman with SB presented to our hospital with decubitus ulcers and was treated by a plastic surgeon. She was referred to our department because of a mass measuring 5 × 4 cm in the superolateral quadrant of the right breast. The size of the right axillary lymph node (LN) was 2 × 1 cm. A core-needle biopsy revealed an invasive ductal carcinoma. Total mastectomy and axillary LN dissection were planned. However, 2 days prior to surgery, the size of the mass and the LN rapidly increased to 7 × 4 cm and 3 × 2 cm, respectively. Furthermore, the enlarged LN was close to the thoracodorsal artery. Since complete resection was difficult, neoadjuvant chemotherapy was also administered. On day 11 of neoadjuvant chemotherapy, the patient was febrile and developed a decubitus ulcer infection at the buttock. The neutrophil count was within normal limits; thus, she was not diagnosed with febrile neutropenia. Follow-up computed tomography revealed a shrinking of the mass to 5 × 4 cm after the first cycle of neoadjuvant chemotherapy. After 17 days of antibiotic therapy and drainage, total mastectomy and axillary LN dissection were performed. Due to the risk of recurrence of infection, adjuvant chemotherapy was discontinued and hormone therapy was initiated. In conclusion, indications for chemotherapy should be carefully evaluated in SB patients with lower limb paralysis and decubitus ulcers.

A Case of Recurrent Ovarian Cancer and Therapy-Related Acute Myeloid Leukemia Treated with Azacitidine.

Therapy-related myelodysplastic syndrome (tMDS) and acute myeloid leukemia (tAML) are lethal complications of chemotherapy. The incidence rates are expected to increase owing to improvements of cancer treatment. Early diagnosis of tMDS/AML is crucial because AML progresses rapidly. Hematopoietic stem cell transplantation (HSCT) is the only current treatment to prolong survival; however, patients with tMDS/AML are more likely to be intolerable to HSCT if they have other active solid tumors. An effective treatment for patients with tMDS/AML who are not candidates for HSCT is not established. We present a case of tAML that developed during chemotherapy for treating active ovarian cancer. The patient presented with thrombocytopenia that was initially suggested to be chemotherapy-induced thrombocytopenia. The patient was not a candidate for HSCT because of active cancer. However, she was able to receive azacitidine because her ovarian cancer responded well to chemotherapy. Pancytopenia is a common symptom of both chemotherapy-induced bone marrow suppression and tMDS/AML; thus, it may be difficult to distinguish between them at the first presentation. Given the prediction that the tMDS/AML incidence will increase as the survival of cancer patients improves, oncologists should be aware of the risks of tMDS/AML in patients with a history of cytotoxic chemotherapy. Although the indications for intensive care of tAML for patients with active solid tumors are poor, some patients might be able to receive cytotoxic treatment for tAML if the active solid tumors remain stable. Further studies focused on tMDS/AML with active solid tumors are needed to develop an effective treatment.