No abstract

This study implies an association of breast cancer risk with the p53 polymorphism Arg72Pro, but not with p73 G4A.

The present study showed risk reduction for Japanese premenopausal women with the CC genotype, but not for postmenopausal Japanese women.

We evaluated the efficacy and safety of sequential therapy with trastuzumab monotherapy (H-mono) followed by H plus docetaxel (D) after disease progression (H --> H + D) versus combination therapy with H + D as first-line therapy. Patients with human epidermal growth factor receptor type 2 (HER2)-positive metastatic breast cancer (MBC) and left ventricular ejection fraction >50% were randomly assigned to either (a) H --> H + D [H, once weekly 2 mg/kg (loading dose, 4 mg/kg); D, once every 3 weeks 60 mg/m(2)] or (b) H + D. Primary endpoints were progression-free survival (PFS) for the H-mono stage of the H --> H + D group and H + D group and overall survival (OS) for both groups. Secondary endpoints were overall response rate, time to treatment failure, second PFS and safety. The planned number of patients was 160 patients in total. Of 112 patients enrolled, 107 were eligible. After 112 patients were enrolled, the Independent Data Monitoring Committee recommended stopping enrollment because PFS and OS were greater in the H + D group than the H --> H + D group. Median PFS was 445 days in the H + D group versus 114 days for H-mono in the H --> H + D group [hazard ratio (HR), 4.24; P < 0.01]. OS was significantly longer in the H + D group (HR, 2.72; P = 0.04). H + D therapy is significantly superior to H --> H + D therapy as first-line therapy in patients with HER2-positive MBC, especially in terms of OS.

Summary Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m2) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.Electronic supplementary materialThe online version of this article (doi:10.1007/s10637-017-0486-4) contains supplementary material, which is available to authorized users.

The present study suggested that any association of the COMT polymorphism with breast cancer risk is limited in Japanese.

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5′ ′ ′ ′ promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5-50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58-1.64) for TC-genotype and 0.81 (0.39-1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother/sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5′ ′ ′ ′ promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.Key words: Breast cancer -CYP17 -Polymorphism -Case-control study CYP17 gene located on chromosome 10q24.3 encodes an enzyme, cytochrome p450c17, which has two different roles in steroid hormone metabolism; 17α-hydroxylase and 17,20-lyase activities. The former converts pregnenolone to 17-hydroxypregnenolone and progesterone to 17-hydroxyprogesterone, and the latter further converts the metabolites to dehydroepiandrosterone and androstenedione, respectively. 1) Since this enzyme is essential for estrogens synthesis, increased or decreased activities are speculated to modify the risk of breast cancer. A single nucleotide polymorphism (T-to-C transition) of CYP17 at 34 bp upstream of the translation initiation site in the 5′ untranslated region was reported to create an additional Sp1-type (CCACC box) promoter site, 2) which suggested an increased rate of transcription and possibly a consequent increase in activity of estrogens. To date, several studies have examined the association of the polymorphism with breast cancer risk, but the results were inconsistent. [3][4][5][6][7][8][9][10][11] Although the incidence of breast cancer in Japan is only one-fifth of that in the United States, it has been increasing since 1960s.12) Second-generation Japanese Americans in Hawaii and Los Angeles have the same level of breast cancer incidence as other Americans, indicating that lifestyle plays an important role in breast cancer carcinogenesis. However, similarly important are genetic factors which modify the effects of lifestyle factors. In Japan, there have been few studies on the association between genetic polymorphisms and breast cancer risk. This is a case-control study to examine the association of the 5′ promoter re...

Although this is the first report on the association between breast cancer risk and IL-1B C-31T, the observed association seems plausible in a biological sense.