Breast Cancer In Japanese Women Research Articles

Prediction of breast cancer risk by automated volumetric breast density measurement.

Dense breast (DB) is recognized as a breast cancer (BC) risk factor. Although DB is common in Japanese women, the incidence of BC is lower than in Caucasians. We evaluated whether DB is a risk factor or whether there are other risk factors for BC in Japanese women. We retrospectively analyzed 635 BC patients and 999 controls who received a mammography at our hospital between February 2019 and March 2021. Volumetric breast density percentage (VBD%), breast volume (BV), and fibroglandular volume (FGV) were measured using Volpara™, an automated, three-dimensional image analysis program. A VBD% of 7.5% or higher was classified as DB. The association between the VBD%, BV, and FGV, and BC risk were assessed using logistic regression. Of the BC group and the control group, 77% and 79% had DB. The stratified FGV was positively associated with BC risk (odds ratio: 2.84; 95% confidence interval 1.58-5.12; P < 0.001). No significant association was found between either the VBD% or BV and BC risk. The proportion of Japanese women with DB was high, suggesting that DB might not be significantly associated with BC risk. However, our results also suggested that the FGV may be related to BC risk in Japanese women.

Association between mammographic breast composition and breast cancer risk among Japanese women: a retrospective cohort study.

Mammographic breast composition is associated with breast cancer risk. However, evidence in a Japanese cohort investigating this association is scarce. Thus, we aimed to compare breast cancer risk between women with and without dense breasts. All Japanese women who underwent breast cancer screening at a tertiary care academic hospital-affiliated preventive center at least twice with known baseline mammographic breast composition were included in this study. A single-center retrospective cohort study was conducted among 24,863 women who had 125,566 screening opportunities between April 1, 2005, and March 31, 2015. All women were categorized into two groups based on their baseline breast composition: women with dense breasts (13,815) and women with non-dense breasts (11,048). We compared the demographic characteristics between the two groups. After calculating person-years, Cox proportional hazards analyses were performed to estimate the hazard ratio (HR) of developing breast cancer according to breast composition status. During the study period, 358 breast cancer cases were identified. The dense and non-dense groups differed significantly by age, body mass index, family history of breast cancer, physical activity, history of smoking and alcohol consumption, number of pregnancies, and number of deliveries. After adjusting for these factors, Cox proportional hazards analyses showed that women with dense breasts had a significantly higher HR for developing breast cancer than women without dense breasts. The association was even stronger in younger women (≤ 50years old), but it did not achieve statistical significance in older women. Dense breasts at baseline are a risk factor for developing breast cancer in Japanese women. However, this association was only observed in women aged 50years or younger at the time of entry into the screening program.

Association between germline pathogenic variants and breast cancer risk in Japanese women: The HERPACC study.

Approximately 5%–10% of breast cancers are hereditary, caused by germline pathogenic variants (GPVs) in breast cancer predisposition genes. To date, most studies of the prevalence of GPVs and risk of breast cancer for each gene based on cases and noncancer controls have been conducted in Europe and the United States, and little information from Japanese populations is available. Furthermore, no studies considered confounding by established environmental factors and single‐nucleotide polymorphisms (SNPs) identified in genome‐wide association studies (GWAS) together in GPV evaluation. To evaluate the association between GPVs in nine established breast cancer predisposition genes including BRCA1/2 and breast cancer risk in Japanese women comprehensively, we conducted a case‐control study within the Hospital‐based Epidemiologic Research Program at Aichi Cancer Center (629 cases and 1153 controls). The associations between GPVs and the risk of breast cancer were assessed by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models adjusted for potential confounders. A total of 25 GPVs were detected among all cases (4.0%: 95% CI: 2.6–5.9), whereas four individuals carried GPVs in all controls (0.4%). The OR for breast cancer by all GPVs and by GPVs in BRCA1/2 was 12.2 (4.4–34.0, p = 1.74E‐06) and 16.0 (4.2–60.9, p = 5.03E‐0.5), respectively. A potential confounding with GPVs was observed for the GWAS‐identified SNPs, whereas not for established environmental risk factors. In conclusion, GPVs increase the risk of breast cancer in Japanese women regardless of environmental factors and GWAS‐identified SNPs. Future studies investigating interactions with environment and SNPs are warranted.

Reproductive and lifestyle factors related to breast cancer among Japanese women: An observational cohort study.

The incidence of breast cancer among Japanese women is substantially increasing. This study evaluated the effects of reproductive and lifestyle factors with respect to breast cancer overall and separately among pre- and postmenopausal women using data from the Three-Prefecture Cohort Study of Japan.A total of 33,410 women aged 40 to 79 years completed a self-administered questionnaire, which included items about menstrual and reproductive history and other lifestyle factors. The follow-up period was from 1984 to 1992 in Miyagi and 1985 to 2000 in Aichi Prefectures. We used Cox proportional hazards regression models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) after adjusting for confounding factors.After 9.8 mean years of follow-up, 287 cases of breast cancer were recorded. In the overall analysis, later menarche (≥16 years) and parity were significantly associated with a decreased risk of breast cancer, with HRs of 0.69 (95% CI 0.48–0.99) and 0.72 (95% CI 0.52–0.99), respectively. Further, there was a significant decline in the risk of breast cancer with increasing number of birth among parous women (P for trend = .010). On the contrary, a family history of breast cancer in the mother was significantly associated with an increased risk of breast cancer (HR 3.22, 95% CI 1.52–6.84). Analyses based on menopausal status at baseline indicated that height (≥160 cm) and weight (≥65 kg) were significantly associated with an increased risk of postmenopausal breast cancer, with HRs of 1.34 (95% CI 0.72–2.50) and 3.13 (95% CI 1.75–5.60), respectively. Risk associated with BMI significantly differs by menopausal status.Our findings suggest the important role of reproductive factors in the development of breast cancer in Japanese women; however, body mass index (BMI) may have different effects on breast cancer in Japanese women compared with western women.

Study on the Association of some Single Nucleotide Polymorphisms of CYP19A1 Gene with Breast Cancer in Vietnamese Women

The CYP19A1 gene encodes for aromatase P450, which is a key enzyme in estrogen metabolism, catalyzes the conversation of testosterone to estradiol and androstenedione to estrone. It is generally believed that polymorphisms in genes coding for key enzymes involved in these pathways could effect to the activity of enzymes, which can change the level of endogenous hormones. Therefore genetic polymorphisms in hormone-related genes could increase the breast cancer susceptibility. In this study, 60 blood samples of breast cancer women and 50 control populations were analyzed to identify the genotype frequency at SNP loci rs10046 C&gt;T and rs2236722 Trp39Arg (T&gt;C) on CYP19A1 using PCR-RFLP and PCR-CTPP respectively. The data were analyzed to determine the association between these polymorphism loci and susceptibility to breast cancer. The result showed that, the genotype frequencies at SNP rs10046 in the control as: CC (14%), CT (48%), TT (38%), in case group are CC (18.33%) , CT (58.33%) and TT (23.34%); at SNP rs2236722 in the control group: TT (94%), TC (6%), in case group TT (90%), TC (10%). The OR analyses for the gene carrying the CC and TC genotypes compared with TT genotype at both loci (OR=2.01; 95% CI=0.87–4.67 with rs10046 and OR = 1.74; 95% CI= 0.40 – 7.42 with rs2236722) indicated that these SNP loci in CYP19A1 have no effect on breast cancer susceptibility.&#x0D; Keywords&#x0D; Breast cancer, SNP, rs10046, rs2236722, CYP19A1 gene&#x0D; References&#x0D; 1. Bora M. T., Tülin Ö., Halil I. K., Sennur I., Calay Z., Oğuz Ö., Turgay I. (2010), “CYP17 (T-34C) and CYP19 (Trp39Arg) Polymorphisms and their Cooperative Effects on Breast Cancer Susceptibility”, In vivo, 24, pp.71–74.2. Chen C., Sakoda L. C., Doherty J. A., Loomis M. M., Fish S., Ray R. M. (2008), “Genetic variation in CYP19A1 and risk of breast cancer and brocystic breast conditions among women in Shanghai, China”, Cancer Epidemiology Biomarkers Prevention, 17(12), pp.3457–3466.3. Dunning A. M., Dowsett M., Healey C. S., Tee L., Luben R. N., Folkerd E., Novik K. L., Kelemen L., Ogata S., Pharoah P. D., Easton D. F., Day N. E., Ponder B. A. (2004), “Polymorphisms associated with circulating sex hormone levels in postmenopausal women”, J. Natl. Cancer Inst., 96(12), pp.936–945.4. Farzaneh F., Noghabaei G., Barouti E., Pouresmaili F., Jamshidi J., Fazeli A. (2016), “Analysis of CYP17, CYP19 and CYP1A1 gene polymorphisms in Iranian women with breast cancer”, Asian Pacific Journal of Cancer Prevention, 17, pp.23–26.5. Ghisari M., Eiberg H., Long M. (2014), “Polymorphisms in phase I and phase II genes and breast cancer risk and relations to persistent organic pollutant exposure: A case-control study in Inuit women”, Environmental Health, 13(1), pp.19.6. Henderson B. E., Ross R., Bernstein L. (1988), “Estrogens as a cause of human cancer: The Richard and Hinda Rosenthal Foundation award lecture”, Cancer Research, 48, pp.246–253.7. Hirose K., Matsuo K., Toyama T. (2004), “The CYP19 gene codon 39 Trp/Arg polymorphism increases breast cancer risk in subsets of premenopausal Japanese”, Cancer Epidemiol BiomarkPrev, 13, pp.1407–1411.8. Kristensen V. N., Harada N., Yoshimura N., Haraldsen E., Lonning P. E. (2000), “Genetic variants of CYP19 (aromatase) and breast cancer risk”, Oncogene, 19, pp.1329–1333.9. Lunardi G., Piccioli P., Bruzzi P., Notaro R., Lastraioli S., Serra M. (2013), “Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus in postmenopausal women with early breast cancer treated with letrozole”, Breast Cancer Research and Treatment, 137(1), pp.167–174.10. Miyoshi Y., Iwao K., Ikeda N., Egawa C., Noguchi S., (2000), “Breast cancer risk associated with polymorphism in CYP19 in Japanese women”, Int J Cancer, 89, pp.325–328. 11. Pineda B., García-Pérez M.Á., Cano A., Lluch A., Eroles P. (2013), “Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case–Control to a Meta–Analysis of 20.098 Subjects”, PLos One, 8(1), pp.1–9.12. Ralph D. A., Zhao L. P., Aston C. E., Manjeshwar S., Pugh T. W. (2007), “Age-specific association of steroid hormone pathway gene polymorphisms with breast cancer risk”, Cancer, 109, pp.1940–1948.13. Samson M., Rama R., Swaminathan R., Sridevi V., Nancy K. N., Rajkumar T., (2009), “CYP17 (T-34C), CYP19 (Trp39Arg), and FGFR2 (C-906T) polymorphisms and the risk of breast cancer in South Indian women”, Asian Pacific J Cancer Prev, 10, pp.111–116.14. Yang L., Wang X. Y., Li Y. T., Wang H. L., Wu T., Wang B. (2015), “CYP19 gene polymorphisms and the susceptibility to breast cancer in Xinjiang Uigur women”, Genetics and Molecular Research, 14(3), pp.8473–8482.15. Yoshimoto N., Nishiyama T., Toyama T., Takahashi S., Shiraki N., Sugiura H., (2011), “Genetic and environmental predictors, endogenous hormones and growth factors, and risk of estrogen receptor positive breast cancer in Japanese women”, Cancer Science, 102(11), pp.2065–2072.16. Zins K., Mogg M., Schneeberger C., Abraham D., (2014), “Analysis of the rs10046 polymorphism of aromatase (CYP19) in premenopausal onset of human breast cancer”, International Journal of Molecular Sciences, 15(1), pp.712–724.

Dietary acrylamide intake and risk of breast cancer: The Japan Public Health Center-based Prospective Study.

Acrylamide forms during cooking and is classified as a probable carcinogen in humans, mandating the need for epidemiological studies of dietary acrylamide and cancers. However, the risk of dietary acrylamide exposure to breast cancer in Japanese women has not been assessed. We investigated the association between dietary acrylamide intake and risk of breast cancer in the Japan Public Health Center‐based Prospective Study. The present study included 48 910 women aged 45‐74 years who responded to a 5‐year follow‐up survey questionnaire. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. During an average of 15.4 years of follow up, 792 breast cancers were diagnosed. Energy‐adjusted dietary acrylamide intake was not associated with the risk of breast cancer (adjusted hazard ratio for highest versus lowest tertile = .95, 95% confidence intervals: 0.79‐1.14, P‐trend = .58). Further, no significant associations were observed when stratified analyses were conducted by smoking status, coffee consumption, alcohol consumption, body mass index, menopausal status, estrogen receptor status, and progesterone receptor status. In conclusion, dietary acrylamide intake was not associated with the risk of breast cancer in this population‐based prospective cohort study of Japanese women.

Correction to: A comparison of clinicopathological characteristics and long-term survival outcomes between symptomatic and screen-detected breast cancer in Japanese women.

In the original publication of this article, Table1 was published incorrectly with rows out of order under "Distant metastasis (n, %)".

Genetic and environmental factors and serum hormones, and risk of estrogen receptor-positive breast cancer in pre- and postmenopausal Japanese women.

Breast cancer incidence in Japanese women has more than tripled over the past two decades. We have previously shown that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive, HER2-negative subtype. We conducted a case–control study; ER-positive, HER2-negative breast cancer patients who were diagnosed since 2011 and women without disease were recruited. Environmental factors, serum levels of testosterone and 25-hydroxyvitamin D, and common genetic variants reported as predictors of ER-positive breast cancer or found in Asian women were evaluated between patients and controls in pre- and postmenopausal women. To identify important risk predictors, risk prediction models were created by logistic regression models. In premenopausal women, two environmental factors (history of breastfeeding, and history of benign breast disease) and four genetic variants (TOX3-rs3803662, ESR1-rs2046210, 8q24-rs13281615, and SLC4A7-rs4973768) were considered to be risk predictors, whereas three environmental factors (body mass index, history of breastfeeding, and hyperlipidemia), serum levels of testosterone and 25-hydroxyvitamin D, and two genetic variants (TOX3-rs3803662 and ESR1-rs2046210) were identified as risk predictors. Inclusion of common genetic variants and serum hormone measurements as well as environmental factors improved risk assessment models. The decline in the birthrate according to recent changes of lifestyle might be the main cause of the recent notable increase in the incidence of ER-positive breast cancer in Japanese women.

Dietary pattern and breast cancer risk in Japanese women: the Japan Public Health Center-based Prospective Study (JPHC Study).

Evidence that diet is associated with breast cancer risk is inconsistent. Most of the studies have focused on risks associated with specific foods and nutrients, rather than overall diet. In this study, we aimed to evaluate the association between dietary patterns and breast cancer risk in Japanese women. A total of 49 552 Japanese women were followed-up from 1995 to 1998 (5-year follow-up survey) until the end of 2012 for an average of 14·6 years. During 725 534 person-years of follow-up, 718 cases of breast cancer were identified. We identified three dietary patterns (prudent, westernised and traditional Japanese). The westernised dietary pattern was associated with a 32 % increase in breast cancer risk (hazard ratios (HR) 1·32; 95 % CI 1·03, 1·70; P trend=0·04). In particular, subjects with extreme intake of the westernised diet (quintile (Q) Q5_5th) had an 83 % increase in risk of breast cancer in contrast to those in the lowest Q1 (HR 1·83; 95 % CI 1·25, 2·68; P trend=0·01). In analyses stratified by menopausal status, postmenopausal subjects in the highest quintile of the westernised dietary pattern had a 29 % increased risk of breast cancer (HR 1·29; 95 % CI 0·99, 1·76; P trend=0·04). With regard to hormone receptor status, the westernised dietary pattern was associated with an increased risk of oestrogen receptor-positive/progesterone receptor-positivetumours (HR 2·49; 95 % CI 1·40, 4·43; P trend<0·01). The other dietary patterns were not associated with the risk of breast cancer in Japanese women. A westernised dietary pattern is associated with an increased risk of breast cancer in Japanese women.

Abstract P4-01-03: Digital measurement of mammographic density and the risk of overlooking cancer in Japanese women

Abstract Introduction: mammographic density is a strong risk factor for breast cancer and an essential determinant of screening sensitivity, but the breast density of Japanese women has yet to be objectively examined. Single mammographic examination fails to detect approximately half of breast cancers in women with dense breasts. We objectively evaluated mammographic density to clarify the relation between breast density and incidence of breast cancer in Japanese women. Method: We enrolled 269 patients diagnosed with breast cancer and 397 healthy controls, who participated in screening mammography at Showa University Hospital. Breast density was measured using Volpara (a software application which analyses breast composition volumetrically). Results: The average age of both control and breast cancer groups was 55. Of the control group, 308 (78%) were characterized as having dense breasts, being defined as volumetric density grade (VDG) 3 or 4. More than 50% of the total population (all ages) had dense breasts (VDG 3 or 4) and more than 20% were extremely dense (VDG:4). Of the breast cancer patients, 232 (87%) were VDG 3 or 4. 52 (23%) of those with dense breasts showed negative results in single mammography examination. In primary breast cancer patients with dense breasts, 30% of those under age 70, but only 13% of those over age 70, showed no abnormal findings from mammographic examination. Conclusion and Discussion: In comparison of our present results and other papers, In the Japanese control group, 72% of patients had dense breasts (VDG 3 or 4) at age 50 or greater, but in Holland, for example, only 36% of women had breasts classed as dense. 87% of Japanese women with breast cancer had dense breasts, approximately the same ratio (88%) as found in Korea. For Japanese and other Asians, women under 70 years old with dense breasts may warrant additional screening. Citation Format: Sawada T, Ikeda M, Kuwayama T, Akashi ST, Nakamura S. Digital measurement of mammographic density and the risk of overlooking cancer in Japanese women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-01-03.

A comparison of clinicopathological characteristics and survival outcomes between symptomatic and screen detected breast cancer in Japanese women.

4 Background: In Japan from 2000, mammography screening has been introduced into the breast cancer screening for women aged 50 or above, however in the early 2000s, breast cancer screening involved palpation only and mammography combined. Only a few studies have been reported clinicopathological characteristics and survival outcomes of this screening detected breast cancer in Japan. This study evaluated effectiveness of this screening by comparing symptomatic and screen detected breast cancer Methods: From January 2000 to December 2004, 1159 patients were underwent surgery for treatment of breast cancer at single hospital in Japan. Among them, 977 patients were symptomatic and 182 patients were this screen detected, and follow-up was performed from the date of the diagnosis until the date of death or the end of follow-up, March 2015. We retrospectively reviewed the clinical and pathologic data. Results: Screen detected breast cancer was associated with more breast conservation surgery, smaller tumor size, less lymph node involvement, more hormone receptor positive, more non-invasive carcinoma and less adjuvant chemotherapy compared with symptomatic breast cancer (P &lt; 0.05). In univariate analyses, women with screen-detected tumors had improved overall survival compared to women with tumors that were detected symptomatically (10-year OS: 90.6% vs.80.4%, P = 0.01). According to ages, in women older than 50 years women with screen-detected tumors had improved overall survival compared to women with tumors that were detected symptomatically (10-year OS:87.7%vs.76.7%, P = 0.006). Screen detection of all patients was independently associated with improved overall survival outcomes (HR 0.47, P = 0.002, respectively), screen detection in women older than 50 years was also similar (HR 0.494, P = 0.007, respectively). Conclusions: This study showed that early detection in breast cancer screening had led to increase in breast conservation rate, avoidance of axillary lymph node dissection, more hormone receptor positive, avoidance of adjuvant chemotherapy, and improvement of survival rate.

Tamoxifen-induced ovarian hyperstimulation during premenopausal hormonal therapy for breast cancer in Japanese women.

PurposeTamoxifen is an anti-estrogenic drug that is widely used for endocrine-dependent breast cancer as adjuvant hormonal therapy, and its use has been reported to be frequently associated with high levels of serum estradiol. Since the population of premenopausal women receiving tamoxifen therapy is growing in Japan, we retrospectively analyzed the incidence of ovarian hyperstimulation by tamoxifen therapy in Japanese women.MethodsEleven patients who received surgical therapy for endocrine-dependent breast cancer and showed high values of serum estradiol during post-operative tamoxifen therapy were recruited in this study and evaluated by examining the serum concentration of follicular stimulating hormone (FSH) and follicular development.ResultsThe mean age, serum concentrations of estradiol and FSH, and follicular diameter were 41.3 years old, 1015.8 pg/mL, 11.8 mIU/mL, and 3.47 cm, respectively. In 6 cases, multiple follicular development was observed, while the other cases showed single follicular development with a mean serum estradiol level of 848.6 pg/mL and follicular diameter of 4.46 cm. There was no significant difference in age or FSH concentration between the two groups. The mean periods from the start of the single administration of tamoxifen to the initial detection of a high estradiol concentration was 716.5 days.ConclusionsThese findings indicate that tamoxifen could stimulate the ovarian function even after 2-year treatment. Since single and multiple follicular developments with large sizes were observed, dual mechanisms through the inhibition of both negative and positive feedback to the hypothalamic-pituitary-axis can be proposed to explain the adverse effects of tamoxifen on ovarian function.

Association of the single nucleotide polymorphism TNRC9 rs3803662 on mammographic density and estrogen receptor-positive breast cancer risk in Japanese women.

1523 Background: The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We recently created risk prediction models for estrogen receptor (ER)-posi...

Abstract P5-13-07: Genetic polymorphism of estrogen metabolizing enzyme CYP17A1 rs743572 impacts on serum testosterone level in Japanese premenopausal women

Abstract The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We recently demonstrated that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive subtype, and we created risk prediction models for ER-positive breast cancer in both pre- and post- menopausal women using genetic factors (single nucleotide polymorphism (SNP)), environmental risk factors, serum hormones and growth factors by logistic regression analysis. Serum level of testosterone, which is the precursor of estradiol in estradiol synthesis, was found to be a risk predictor in both pre- and post- menopausal women. On the other hand, it has been reported that some SNPs, including those of estrogen-related genes such as ESR1 and CYP17A1, are correlated with breast cancer risk by genome-wide association studies. To acquire some insights into this mechanism, we analyzed genetic factors (14 SNPs), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3)) in 913 women with breast cancer and 278 disease-free controls for correlation between them. Serum testosterone and prolactin levels were significantly higher in ER-positive breast cancer patients than in disease-free controls in both pre- (p&amp;lt;0.0001, p&amp;lt;0.0001) and post- (p&amp;lt;0.0001, p = 0.007) menopausal women, and serum estradiol level was significantly higher in ER-positive breast cancer patients than in disease-free controls only in premenopausal women (p = 0.0005). There were significant differences in serum hormone levels among the women with each SNP genotype (homozygotes of major allele, heterozygotes and homozygotes of minor allele), including testosterone among rs743572 genotype (p = 0.014), estradiol among rs827421 genotype (p = 0.016), IGF-1 among rs6905370 genotype (p = 0.032), and prolactin among rs1042522 genotype (p = 0.035) in premenopausal women, as well as estradiol among rs3803662 genotype (p = 0.027) and IGFBP3 among rs6905370 genotype (p = 0.036) in postmenopausal women. In particular, serum testosterone level was significantly different among the rs743572, which is one of the enzymes that convert testosterone to estradiol, of genotypes (AA: 0.308 +/- 0.180 ng/ml, AG: 0.319 +/- 0.193 ng/ml and GG: 0.380 +/- 0.187 ng/ml, p = 0.014). On the other hand, the rs743572 heterozygotes of CYP17A1 have been reported to have increased breast cancer risk than homozygotes of both the major allele and minor allele in premenopausal women. Further studies are required to clarify this mechanism. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-07.

Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study

The purpose of this study is to evaluate how beverages containing Lactobacillus casei Shirota (BLS) and soy isoflavone consumption since adolescence affected the incidence of breast cancer. In a population-based case-control study, three hundred and six cases with breast cancer and 662 controls aged 40 to 55 were matched for age and residential area and included in the analyses. Diet, lifestyle and other breast cancer risk factors were investigated using the self-administered questionnaire and interview. Odds ratios (ORs) of BLS and soy isoflavone consumption for breast cancer incidence were independently and jointly estimated using a conditional logistic regression. The ORs of BLS consumption (≥ four times a week against < four times a week) was 0.65 and statistically significant (p = 0.048). The analysis of association between soy consumption and breast cancer incidence showed the more the isoflavone consumption is, the lower the odds of breast cancer becomes. Adjusted ORs for breast cancer in the second, the third and the fourth quartiles of soy consumption against the first quartile were 0.76, 0.53 and 0.48, respectively (trend test, p = 0.0002). The BLS-isoflavone interaction was not statistically significant; however, a biological interaction was suggested. Regular consumption of BLS and isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women.

Dietary cadmium intake and breast cancer risk in Japanese women: A case–control study

Cadmium, an environmental pollutant, may act like an estrogen and be a potential risk factor for estrogen-dependent diseases such as breast cancer. We examined the hypothesis that higher dietary cadmium intake is associated with risk of overall and hormone receptor-defined breast cancer in Japanese women, a population with a relatively high cadmium intake. The study was conducted under a case-control design in 405 eligible matched pairs from May 2001 to September 2005 at four hospitals in Nagano Prefecture, Japan. Dietary cadmium intake was estimated using a food frequency questionnaire. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer and its hormone-receptor-defined subtypes were calculated by tertile of dietary cadmium intake. We found no significant association between dietary cadmium and risk of total breast cancer in either crude or multivariable-adjusted analysis. Adjusted ORs for tertiles of cadmium intake were 1.00, 1.19, and 1.23 (95% CI, 0.76-2.00; P for trend=0.39) for whole breast cancer. Further, no significant associations were seen across strata of menopausal status, smoking, and diabetes in multivariable-adjusted models except for adjusted OR for continuous cadmium intake in postmenopausal women. A statistically significant association was found for estrogen receptor-positive (ER+) tumors among postmenopausal women (adjusted OR=1.00, 1.16, and 1.94 [95% CI, 1.04-3.63; P for trend=0.032]). Although the present study found no overall association between dietary cadmium intake and breast cancer risk, higher cadmium intake was associated with increased risk of ER+ breast cancer in postmenopausal women, at least at regular intake levels in Japanese women in the general population. Further studies are needed to confirm this association.

Cadmium exposure and the risk of breast cancer in Japanese women

Non-occupational exposure to cadmium has been suspected to be a risk factor for breast cancer. The present study examined the association between urinary cadmium level and the risk of breast cancer in a case-control study among Japanese women. Cases were 153 women newly diagnosed and histologically confirmed with breast cancer at a general hospital in Gifu, Japan. A total of 431 controls individually matched to cases by age, menopausal status, and the period of urine sampling were selected from those who attended a breast cancer mass screening at this hospital. Urinary cadmium levels were measured using spot urine samples. Spot urine samples were collected from cases after surgery but before any cancer therapy. For controls, spot urine samples were obtained at the date of the screening visit. Information on known or suggested breast cancer risk factors was obtained by a self-administered questionnaire. The odds ratios (ORs) and 95 % confidence intervals (CIs) of breast cancer according to the tertile of the creatinine-adjusted cadmium level were calculated using conditional logistic regression models. Women in the highest tertile of the creatinine-adjusted cadmium level (>2.620 μg/g) had significantly elevated OR of breast cancer relative to those in the lowest tertile (<1.674 μg/g) after controlling for covariates [OR = 6.05, (95 % CI 2.90, 12.62)]. The trend of increase in risk with increasing cadmium level was also statistically significant [OR = 1.67, (95 % CI 1.39, 2.01) for every 1.0 μg/g increase in urinary cadmium level, P-trend <0.01]. These data suggested that exposure to cadmium was associated with a risk of breast cancer in Japanese women.

Abstract P4-12-06: A mammographic density prediction model using environmental factors, endogenous hormones and growth factors in Japanese women

Abstract The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades, making it important to evaluate breast cancer risk factors in Japanese women. It is well known that mammographic density is positively associated with breast cancer risk in Western countries, and mammographic density is known to be affected by some environmental factors, serum hormones, and growth factors. We performed stepwise variable selection in a multiple regression model with fifteen independent variables as described below, based on the Akaike information criteria (AIC) to build a mammographic density prediction model using a dataset of 1191 women (913 women with breast cancer and 278 disease-free controls). The variables included were: environmental risk factors (body-mass index (BMI), age at menarche, pregnancy, age at first birth, breastfeeding, family history of breast cancer, age at menopause, use of hormone replacement therapy, alcohol intake and smoking), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3)) and mammographic density. The resulting prediction model is: Mammographic density = + 0.000476 (IGF1) −0.0605 (testosterone) − 0.0508 (IGFBP3) − 0.00683 (age) − 0.0175 (BMI) + 0.00883 (age at menarche) − 0.0153 (breast feeding), (R2 = 0.336). In this model, IGF1, testosterone, IGFBP3, age, BMI, age at menarche, and breastfeeding were considered to be important factors. IGF1 and age at menarche were positively associated with mammographic density, while on the other hand testosterone, IGFBP3, age, BMI, and breast feeding were negatively associated with mammographic density. Further studies are required to build a modified model incorporating serial measurements of serum hormones and growth factors to take into account time-dependent changes of serum hormones and growth factors, and to assess its accuracy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-06.

Reproductive and hormonal risk factors for luminal, HER2-overexpressing, and triple-negative breast cancer in Japanese women

Although the clinical relevance of the molecular subtypes of breast cancer is evident, etiological differences among subtypes have not been well established, especially among Asian. Here, we evaluated the hypothesis that the etiologic impact of reproductive and hormonal features differs among molecular subtypes. We conducted a case-control study in pre- and postmenopausal Japanese. We examined 706 breast cancer patients and 1412 age- and menopausal status-matched noncancer controls. Immunohistochemical stains for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were used to classify the cases into 554 luminal (hormone receptor positive), 84 HER2-overexpressing (hormone receptor negative, HER2 positive), and 68 triple-negative cases (hormone receptor negative, HER2 negative). Associations were evaluated using multivariate polytomous logistic regression models. A significant association was observed between early age at menarche and risk of luminal disease (odds ratios = 1.67, 95% confidence interval: 1.22-2.29; P trend = 0.001). No significant differences in association with parity, age at first live birth, breastfeeding history, age at menopause, or synthetic hormonal use were seen across molecular subtypes of breast cancer. These findings indicate that reproductive events in adolescence have differential impact on the risk of breast cancer molecular subtypes in Japanese.

Harms of screening mammography for breast cancer in Japanese women

The US Preventative Services Task Force assesses the efficacy of breast cancer screening by the sum of its benefits and harms, and recommends against routine screening mammography because of its relatively great harms for women aged 40-49years. Assessment of the efficacy of screening mammography should take into consideration not only its benefits but also its harms, but data regarding those harms are lacking for Japanese women. In 2008 we collected screening mammography data from 144,848 participants from five Japanese prefectures by age bracket to assess the harms [false-positive results, performance of unnecessary additional imaging, fine-needle aspiration cytology (FNA), and biopsy and its procedures]. The rate of cancer detected in women aged 40-49years was 0.28%. The false-positive rate (9.6%) and rates of additional imaging by mammography (5.8%) and ultrasound (7.3%) were higher in women aged 40-49years than in the other age brackets. The rates of FNA (1.6%) and biopsy (0.7%) were also highest in women aged 40-49years. However, they seemed to be lower than the rates reported by the Breast Cancer Surveillance Consortium (BCSC) and other studies in the US. The results, although preliminary, indicate the possibility that the harms of screening mammography for Japanese women are less than those for American women.