Breast Cancer

We encountered a very rare case of occult breast cancer associated with paraneoplastic sensory polyneuropathy. A 59-year-old woman was admitted to our hospital complaining of numbness in all extremities, ataxia of left extremities and a tumor in the left axilla. From the neurological findings, a malignant tumor was suspected. The immunohistochemical analysis of the axillar swollen lymph node revealed metastasis from breast cancer and confirmed the primary lesion. On a preoperative diagnosis of suspected occult breast cancer, left mastectomy and resection of left axillar lymph nodes were performed. Furthermore, immunohistochemical staining of sural nerves and Western blot analysis of the serum of this patient showed the loss of axons and the presence of antineural antibody in the serum. Immunological response was considered to be the remote effector system between the breast cancer and sensory polyneuropathy in this disorder.

The aim of healthcare providers is to help patients regain their health and/or maintain or increase their happiness. The quality of healthcare can be assessed objectively by using indices such as survival rates, but subjective assessment is sometimes more important than objective evaluation, because whether patients feel healthy or happy or not is their major concern. Quality of life (QOL) research is a typical approach to subjective assessment of health. Self-administered health-related QOL (HRQOL) questionnaires are used to obtain patient-reported outcome (PRO) data. PRO is defined by the US Food and Drug Administration (FDA) as any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else. PRO data are regarded as more accurate than clinician-rated ones in terms of assessing patients’ symptoms and HRQOL. The Comprehensive Support Project for Health Outcome Research of the Public Health Research Foundation has conducted much PRO research in collaboration with the Comprehensive Support Project for Oncology Research, especially in randomized controlled trials (RCTs). Here, we review the results of PRO research in RCTs conducted in Japan and examine future perspectives in this field.

The purpose of this study was to determine the usefulness of sequential FDG PET/CTs for prediction of axillary lymph node (ALN) status after neoadjuvant chemotherapy (NAC). Seventy-seven stage II or III breast cancer patients who received 3 cycles of neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for early metabolic response prediction. Patients with pN0 had significantly lower post-NAC ALN standard uptake value (SUV) than those who were pN+ (1.22 ± 1.46 in pN0 vs. 2.13 ± 1.99 in pN+, P = 0.017). Post-NAC ALN size on CT also differed according to pathologic ALN status (6.3 mm in pN0 vs. 11.1 mm in pN+, P = 0.014). When serial FDG PET/CT and chest CT were used, patients with an SUV > 1.5 and post-NAC ALN size ≥10 mm on CT did not achieve pN0 (specificity 100% and positive predictive value 100%). The serial FDG PET/CT after NAC could predict the pathologic status of ALN before surgery in stage II/III breast cancer. Our findings suggest that the combined use of serial FDG PET/CTs and chest CT might provide better information regarding ALN before surgery.

BRCAness is characterized as the phenotypes shared between some sporadic tumors and BRCA1/2 mutation cancers resulting in defective homologous recombination. The predictive or prognostic value of BRCAness in HER2-negative breast cancer patients who have received neoadjuvant chemotherapy (NAC) is not fully elucidated. We retrospectively selected 101 high-risk HER2-negative patients diagnosed with stage I–III breast cancer who underwent NAC treatment and evaluated BRCA1-like phenotype using multiplex ligation-dependent probe amplification assay. In an analysis of BRCAness, 95 out of 101 patients were analyzed. In total, 70 (74%) patients had sporadic-type tumors and 25 (26%) had BRCA1-like tumors according to pre-treatment samples. The BRCA1-like phenotype was not associated with pathological complete response (pCR) rate in the entire cohort. In survival analysis, pre-treatment BRCA1-like phenotype was not associated with survival. On the other hand, post-treatment BRCA1-like patients apparently showed shorter relapse-free survival (log-rank P = 0.016) and breast cancer-specific survival (P < 0.001) compared with sporadic features. In multivariate analysis, only the post-treatment BRCA1-phenotype was significant prognostic factors (HR 5.67, 95% CI 1.19–29.3). Furthermore, we found phenotype change between BRCA1-like and sporadic type through NAC in 19% of non-pCR patients. Post-treatment Ki67 significantly decreased in the persistent sporadic tumors during treatment or sporadic tumors changed after NAC (P < 0.0001, P = 0.0078, respectively). BRCAness may be useful biomarkers to predict prognosis for HER2-negative breast cancer refractory to standard chemotherapy. Our results pave the way for identifying patients who require alternative therapies.

TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor, and fibroblast growth factor receptor. This open-label, non-comparative, multicenter phase II study evaluated TSU-68 in combination with docetaxel in patients with metastatic breast cancer that had relapsed within 1 year despite prior treatment with an anthracycline-containing regimen. TSU-68 was orally administered on days 1–21, and docetaxel was intravenously delivered on day 1. The regimen was repeated every 21 days. Primary endpoint was objective response rate according to the RECIST guidelines version 1.0. TSU-68 in combination with docetaxel produced objective responses in 21.1% and clinical benefits in 42.1% of the patients, respectively (1 complete response, 3 partial response, and 4 stable disease for at least 24 weeks, n = 19). Median time to progression was 148 days, and median overall survival was 579 days. The common adverse drug reactions were leukopenia, neutropenia, nail disorder, malaise, dysgeusia, alopecia, and edema. TSU-68 in combination with docetaxel showed a promising antitumor response with manageable toxicity in patients with anthracycline-resistant metastatic breast cancer. Further studies are warranted in a different population of breast cancer or other solid cancers.

Randomized clinical trials demonstrate that lumpectomy + hormone therapy (HT) without radiation therapy (RT) yields equivalent survival and acceptable local–regional outcomes in elderly women with early-stage, node-negative, hormone-receptor positive (HR +) breast cancer. Whether these data apply to men with the same inclusion criteria remains unknown. The National Cancer Database was queried for male patients ≥ 65 years with pathologic T1-2N0 (≤ 3 cm) HR + breast cancer treated with breast-conserving surgery with negative margins from 2004 to 2019. Adjuvant treatment was classified as HT alone, RT alone, or HT + RT. Male patients were matched with female patients for OS comparison. Survival analysis was performed using Cox regression and Kaplan − Meier method. Inverse probability of treatment weighting (IPTW) was applied to adjust for confounding. A total of 523 patients met the inclusion criteria, with 24.4% receiving HT, 16.3% receiving RT, and 59.2% receiving HT + RT. The median follow-up was 6.9 years (IQR: 5.0–9.4 years). IPTW-adjusted 5-yr OS rates in the HT, RT, and HT + RT cohorts were 84.0% (95% CI 77.1–91.5%), 81.1% (95% CI 71.1–92.5%), and 93.0% (95% CI 90.0–96.2%), respectively. On IPTW-adjusted MVA, relative to HT, receipt of HT + RT was associated with improvements in OS (HR: 0.641; p = 0.042). RT alone was not associated with improved OS (HR: 1.264; p = 0.420). Among men ≥ 65 years old with T1-2N0 HR + breast cancer, RT alone did not confer an OS benefit over HT alone. Combination of RT + HT demonstrated significant improvements in OS. De-escalation of treatment through omission of either RT or HT at this point should be done with caution.

The Cytology and Core Needle Biopsy Subcommittee, organized under the Rules Committee of the Japanese Breast Cancer Society, has prepared a new form for breast cytology reports. This reporting form consists of “diagnostic categories” and “recommendations.” The “diagnostic category” is either “specimen inadequacy” or “specimen adequacy.” The judgment on “specimen adequacy” is subdivided into four categories: “normal or benign,” “indeterminate,” “suspicious for malignancy,” and “malignant.” The “recommendation” indicates descriptions of cytological features and estimated histological type of tumor (these descriptions should be as detailed as possible). On the basis of an analysis of cytological data from 3,439 cases performed before preparing this form, the subcommittee has attached the following recommended goals to this form: (1) the percentage of “specimen inadequacy” should be 10% or less of all samples, (2) the percentage of “indeterminate” samples should be 10% or less of all “specimen adequacy” cases, and (3) 90% or more of “suspicious for malignancy” cases should be diagnosed as “malignant” in a subsequent histological examination. We hope that modification of this form, if it requires revision in the future, will be evidence-based, as was the process for compiling this set of rules.

A case of breast cancer that metastasized to the head of the pancreas 6 years and 8 months after mastectomy is reported. The pancreas head metastasis was associated with general fatigue and obstructive jaundice. The serum levels of CEA, CA15-3 and NCC-ST-439, tumor markers of breast cancer, were within normal limits, but CA15-3 was immunohistochemically demonstrated in the resected metastatic lesion, in a manner similar to lobular carcinoma of the breast.

Lobular carcinoma of the breast presents with various clinical manifestations. Lobular carcinoma comprises about one fifth of cases of ductal carcinoma. Intestinal metastasis is dominant in cases of lobular carcinoma. Without a prior diagnosis of lobular carcinoma of the breast, the diagnosis of intestinal metastasis from breast cancer is difficult. A 52-year-old women underwent duodenogastrectomy for duodenal cancer. About 18 months later, she underwent mastectomy for lobular carcinoma of the breast. The duodenal cancer consisted mainly of malignant cells invading the submucosa that were identical to those in the breast. Immunohistochemical assays for estrogen receptor also confirmed breast cancer metastasis. Duodenal obstruction was the first sign of isolated metastatic lobular carcinoma of the breast in this case. The characteristic metastatic pattern of lobular carcinoma, which differs from that of ductal carcinoma, should be kept in mind to ensue proper diagnosis. Preceding breast surgery for lobular carcinoma should prompt investigation based on the typical metastatic pattern.