Misako Nakagawa

The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia.

BackgroundThe clinical predictors of aromatase inhibitor-related arthralgia (AIA), a drug-related adverse reaction of aromatase inhibitors (AIs), remain unclear.MethodsAIA was prospectively surveyed every 4 months in 328 postmenopausal breast cancer patients administered a non-steroidal AI (anastrozole). Various clinicopathological parameters were recorded and analyzed (chi-square test, Fishers exact test and logistic regression analysis).ResultsThe mean observation period was 39.9 months. AIA manifested in 114 patients (34.8%), with peaks of onset at 4 (33.7%) and 8 months (11.4%) after starting AI administration. Some cases manifested even after 13 months. AIA tended to occur in younger patients (incidences of 46.3%, 37.4% and 28.0% for ages of < 55, 55-65 and > 65 years, respectively (p = 0.063)) and decreased significantly with the age at menarche (53.3%, 35.3% and 15.4% for < 12, 12-15 and > 15 years, respectively (p = 0.036)). The incidences were 45.1%, 46.3 and 25.1% for the time since the last menstrual period (LMP) < 5 years, 5-10 years and > 10 years, being significantly lower at > 10 years (p < 0.001). In logistic regression analysis, the AIA incidence was significantly lower in the time since LMP > 10-year group versus the < 5-year group (odds ratio 0.44, p = 0.002), but the age at menarche showed no association. AIA manifested significantly earlier (≤ 6 months) as the time since LMP became shorter (< 5 years).ConclusionAIA tends to manifest early after starting AI, but some cases show delayed onset. The incidence was significantly lower in patients with a duration of > 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration.

Joint Symptoms, Aromatase Inhibitor-Related Adverse Reactions, Are Indirectly Associated with Decreased Serum Estradiol

Background. Joint symptoms (JSs) are problematic adverse drug reactions (ADRs) of aromatase inhibitors (AIs). Involvement of decreased serum estradiol (SE) has been suggested. Patients and Methods. 104 postmenopausal breast cancer patients administered an AI were prospectively investigated regarding various clinical parameters, JS and hot flashes as ADRs, and the SE level. Results. JS manifested in 31.7% of patients and hot flashes in 18.3%. Chi-square testing showed a significantly higher incidence of JS in several patient strata: <55 years old, decreased SE, and elevated total cholesterol (TC). In univariate analysis, JS correlated significantly with a pre-AI % YAM of ≥80%, decreased SE, and elevated TC. Eight (7.7%) patients maintained SE at ≥5 pg/mL for >6 consecutive months, with no JS. In chi-square testing, hot flashes showed a significantly higher incidence in patients <55 years old. Conclusion. AI-ADRs occurred more readily in younger patients. Decreased SE may be indirectly involved in JS.

Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis

Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.

Molecular Diagnosis and Targeting Therapy for Breast Cancer

Breast cancer (BC) is a representative cancer for which molecular targeting therapy is most popular, because systemic therapy is selected according to tumor biological subtypes, luminal A, luminal B, HER2-enriched, and basal-like; those are decided by gene expression pattern or estrogen receptor (ER), HER2, and tumor proliferation measured by Ki67 expression in immunohistochemistry. Approximately 70–80% of BC is ER positive. Adjuvant therapy is selected according to the guideline based on the large-scale randomized control trials. Selective estrogen receptor modulators (SERM), like tamoxifen or toremifene, and gonadotropin-releasing hormone agonist (GnRH) are used in combination or alone for premenopausal metastatic BC (MBC) and in adjuvant setting. Aromatase inhibitor (AI) targeting the enzyme aromatase is recommended for postmenopausal BC in adjuvant and MBC both in pre- and postmenopausal.

Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)

Micro‐Abstract Efficacy of S‐1 (Taiho Pharmaceutical Co, Tokyo, Japan) used in combination with docetaxel (S‐1+DOC) for breast cancer was evaluated. After 4 cycles of S‐1+DOC, patients with a complete response (CR) underwent surgery, and those with partial response underwent 4 more cycles. Patients with stable disease or progressive disease received epirubicin and cyclophosphamide or trastuzumab and paclitaxel. The pathological CR rate was 29 patients [34.9%], and 8 patients [19.5%] for patients with luminal type breast cancer. S‐1+DOC was expected to be an effective chemotherapy for luminal type breast cancer. Background: To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S‐1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low‐dose docetaxel (S‐1+DOC) were evaluated. Patients and Methods: Patients were treated with docetaxel (40 mg/m2 intravenously on day 1) and S‐1 (40 mg/m2 orally twice per day on days 1‐14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S‐1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. Results: Ninety‐four patients entered the study. After 4 cycles of S‐1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple‐negative group. Conclusion: The S‐1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.