Risk Of Bilateral Breast Cancer Research Articles

The study of genetic and clinicopathological characterisation of Turkish bilateral breast cancer patients

Introduction. Although bilateral breast cancers are a rare condition in the general population, the incidence has increased significantly in BRCA1 and BRCA2 gene carrier breast cancer patients. Besides the genetic susceptibility, many risk factors such as age, first breast cancer diagnosis age, lifestyle, and environmental factors may be effective in the development of this type of cancer. This study aimed to determine BRCA1/2 gene carriage in patients with bilateral breast cancer and to find out the risk factors that may lead to contralateral cancer formation. Material and methods . From 2016 to 2018, in Turkey, we grouped 31 women diagnosed with bilateral breast cancer synchronously and metasynchronously. Analysis of BRCA1 and BRCA2 genes of these women evaluated for clinical and pathological tumour characteristics was performed using the NGS technique. Results. No significant difference was found between the metachronous (MBBC) and synchronous (SBBC) groups in terms of clinical and pathological tumour characteristics. MBBC patients’ age at first diagnosis of breast cancer was lower than SBBC. Also, there was a statistically significant relationship between chronic diseases and MBBC cancers (c2 = 11.519; p = 0.001). In our study, disease-related variants were found only in three patients, and two of these variants were identified the first time in the literature. Conclusion. The risk of bilateral breast cancer of BRCA1/2 carriers increases when the first breast cancer is diagnosed at a young age and there is a significant family history of cancer. MBBC is associated with chronic diseases, and large-scale research will contribute to clarifying this relationship.

High relative levels of satellite alpha transcripts predict increased risk of bilateral breast cancer and multiple primary cancer in patients with breast cancer and lacking BRCA‑related clinical features

Patients with breast cancer who undergo surgery have a risk of developing multiple cancers in the contralateral breast and other organs. We previously reported that overexpression of satellite alpha transcripts (SAT) facilitates chromosomal instability, which is involved in the development of multiple tumors in patients with colorectal and gastric cancer. In this study, we elucidated the significance of SAT in the development of multiple tumors in patients with breast cancer. Relative expression of SAT (rSAT) was calculated in normal and tumor tissues from 167 patients. In total, 27 patients developed bilateral breast cancer (BBC) and 27 patients showed multiple primary cancer (MPC), with patients with BBC and MPC showing higher rSAT levels in tumor tissues than those in patients with single breast cancer (SBC) (P=0.0312 and P=0.0420, respectively). Additionally, higher rSAT levels in tumor tissues from patients with BBC were a significant factor according to univariate analysis, and multivariate analysis showed that rSAT >1.5 was a significant predictor of MPC [hazard ratio (HR): 2.96; P=0.0243); however, we did not clarify the involvement of SAT in normal tissues. Excluding 71 patients with BRCA‑related clinical features, rSAT levels were higher in patients with BBC and MPC than in patients with SBC in tumor tissues and normal tissues (P<0.05). Significant predictors according to univariate analysis included rSAT >1.5 in tumor tissues, rSAT >2.4 in normal tissues, and T <2, whereas those for multivariate analysis included rSAT >2.4 in normal tissues for BBC (HR: 22.7; P=0.00120) and MPC (HR: 13.0; P=0.00601). Our data indicated that patients with breast cancer and high rSAT levels in their breast tissues exhibit a 10‑ to 20‑fold increased risk for the development of multiple cancers when harboring no BRCA‑related clinical features.

Satellite alpha transcript levels to predict risk of bilateral breast cancer and multiple primary cancer in patients with breast cancer who lack BRCA-related clinical features.

e12575 Background: Patients with breast cancer who undergo surgery have a risk of developing multiple cancers in the contralateral breast and other organs. We have reported that the overexpression of satellite alpha transcripts (SAT) facilitates chromosomal instability, which is involved in the development of multiple tumors in patients with colorectal and gastric cancer. Methods: In this study, we elucidated the significance of SAT in the development of multiple tumors in patients with breast cancer. Relative expression SAT (rSAT) level was calculated in normal and tumor tissues from 167 patients. Twenty-seven patients developed bilateral breast cancer (BBC) and 27 patients showed multiple primary cancer (MPC). We detected that 71 patients had factors associated with inherited breast cancer; age under 50yo, harboring family history of breast cancer, pathological diagnosis of TNBC, and history of ovarian cancer and we determined these factors as BRCA-related clinical factors. Results: We excluded 71 patients with BRCA-related clinical features, rSAT levels were higher in patients with BBC and MPC than in patients with SBC in tumor tissues ( P = 0.0121) and normal tissues ( P = 0.00586). A univariate analysis indicated significant predictors including rSAT &gt; 1.5 in tumor tissues, rSAT &gt; 2.4 in normal tissues. In a multivariate analysis, rSAT &gt; 2.4 in normal tissues was a significant predictor of BBC (HR, 22.7; P = 0.00120) and MPC (HR, 11.1; P = 0.00885). Conclusions: Our data indicated that patients with breast cancer with high rSAT levels in their breast tissues have a 10- to 20-fold increased risk for the development of multiple cancers when they harbored no BRCA-related clinical features. These patients had been excluded from the high-risk group for BBC, however, our results shed light on these patients and we detected another risk factor which could predict multiple cancers.

Precursors of Breast Cancer

It has become apparent that estrogen receptor (ER) - positive and - negative breast lesions are completely distinct diseases. Precursors of low-grade breast cancer are low-grade premalignant lesions, usually ER and progesterone receptor (PR) positive and HER2 negative. On the other hand, precursors of high-grade breast cancer are high-grade premalignant lesions, usually ER and PR negative and HER2 positive. Lobular neoplasia (LN) and ductal carcinoma in situ (DCIS) are important from the clinical point of view. LN increases the risk of bilateral breast cancer. This is why the recommendation for the treatment of LN is very different - from just following up up to bilateral mastectomy. The complete surgical excision of the lesion with negative margins is the usual treatment of DCIS. Several big randomized clinical trials showed the benefit of adjuvant radiotherapy (RT). Some of them suppose that there is a group of patients who do not need adjuvant treatment. The benefit of adjuvant tamoxifen is clear only for patients with ER positive disease. The UK/ ANZ study showed the benefit of tamoxifen only in patients without RT.

Common genomic variants associated with breast cancer predict the risk of second primary breast cancer diagnosis

Background A diagnosis of a second primary breast cancer (‘bilateral breast cancer’) occurs in between 2-11% of women affected by breast cancer in the general population, but is increased in frequency in women with a family history of breast cancer. We investigated whether the common genomic variants described in breast cancer GWAS studies were determinants of the risk of bilateral breast cancer and compared the effect to that of family history.

Frequency of the CHEK2 1100delC mutation among women with early-onset and bilateral breast cancer

We read with great interest the recent Breast Cancer Research paper by Desrichard and colleagues [1] reporting the association between CHEK2 mutations and non-BRCA hereditary breast cancer risk. This report summarized the results of different case-control studies to provide an overview of CHEK2 1100delC mutation and susceptibility to early-onset breast cancer (EOBC) and bilateral breast cancer (BBC). We believe there are significant issues to note regarding the authors' study. To investigate the role of CHEK2 1100delC mutation in BBC susceptibility, Desrichard and colleagues performed a systematic review and pooled analysis based on five studies. Notably, another study that showed contradictory results indicating that the 1100delC mutation might not be a modifier in BBC [2] was not included in these analyses. Rashid and colleagues [3] have also shared their data, which failed to identify CHEK2 1100delC mutations among cases of BBC. Interestingly, the study by de Jong and colleagues [4] categorized individuals with BBC as unselected breast cancer cases. However, the BBC cases were included in the group of 192 patients identified with early-onset/familial breast cancer from an Irish study [5]. Hence, ongoing uncertainty exists and, in our opinion, the conclusion reached by Desrichard and colleagues may not be fully supported by the available data. An additional issue is the association between CHEK2 mutations and EOBC risk. Using the same search strategy as that of Desrichard and colleagues, we located three relevant case-control studies in PubMed comprising a total of 3,742 EOBC cases and 8,405 controls [6-8], which were not included in the pooled analyses. Furthermore, we have combined all of the studies on European populations into a new pooled analysis. By using a fixed-effect model, significant associations were found to be associated with CHEK2 1100delC mutation in patients with EOBC (odds ratio 3.14, 95% confidence interval 1.86 to 5.28). In conclusion, the association between CHEK2 1100delC mutation and BBC risk may be complex, and further studies will likely be needed to clarify the correlation of BBC and familial breast cancer characteristics. Similarly, further studies on EOBC-specific populations would be helpful for the purpose of better evaluating the association between CHEK2 1100delC mutation and EOBC risk.

Clinical characteristics and outcomes of bilateral breast cancer in an Australian cohort

Purpose Uncertainty remains about the impact of bilateral breast cancer. Characteristics and outcomes of unilateral and bilateral breast cancer were compared within an Australian multi-institutional cohort. Methods Demographic, tumour and treatment characteristics were compared among unilateral ( n = 2336) and bilateral cases (52 synchronous, 35 metachronous) using descriptive analyses. Disease-specific outcomes were investigated using Cox regression modelling to adjust for prognostic and treatment factors. Results Factors associated with increased risk of bilateral breast cancer included lobular histology ( p = 0.046), family history ( p = 0.025) and metropolitan residence ( p = 0.006). Mastectomy was more common for bilateral cases ( p = 0.001) while radiotherapy was less common ( p = 0.015). Index metachronous cases were less likely to receive hormonal therapy ( p = 0.001). Five-year survivals for metachronous, synchronous and unilateral cases were 79%, 88% and 94%, respectively. Poorer outcomes remained after adjusting for prognostic factors [HR = 2.26, 1.21–4.21]. Conclusion Our results confirm international findings indicating worse outcomes from bilateral compared with unilateral breast cancer.

Breast Cancer Onset in Twins and Women With Bilateral Disease

Little is known of the onset of breast cancer in high-risk populations. We investigated the risk of breast cancer in twin sisters and in the contralateral breast taking family history into consideration. We analyzed a Scandinavian population-based cohort of 2,499 female twin pairs, in which at least one had a diagnosis of breast cancer and estimated the risk of breast cancer in the sister. Using a total of 11 million individuals in Sweden with complete family links, we identified 93,448 women with breast cancer and estimated the risk of a bilateral breast cancer. The incidence of breast cancer in twin sisters of breast cancer patients was 0.64% per year and 0.42% per year in mono- and dizygotic twin sisters, respectively. In comparison, the risk of familial (affected first-degree relative) and nonfamilial bilateral breast cancer was 1.03% per year and 0.68% per year, respectively. Contrary to the risk of unilateral disease, the risk of cancer in the nonaffected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (incidence rate ratio [IRR] = 1.52; 95% CI, 1.42 to 1.64) and the relative risk in the dizygotic twin sister was 25% lower (IRR = 0.75; 95% CI, 0.61 to 0.91) compared with the risk of nonfamilial bilateral cancer. The elevated risk of breast cancer in high-risk groups is little affected by age and time since diagnosis. Our findings suggest that susceptible groups of women might have already aggregated genetic prerequisites for breast cancer.

Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma

Background Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC. Methods A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups. Results The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group ( P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC. Conclusions BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.

Human Leukocyte Antigen as a Predictive Factor of Developing Bilateral Breast Cancer in Japanese Women

To investigate the relationship between human leukocyte antigen (HLA) type and bilateral breast cancer, a total of 213 female breast cancer patients were entered into this study. The lymphocyte cytotoxicity test was used for HLA typing. HLA frequency and haplotype antigen frequency were calculated with a microcomputer. A chi-squared test was used for comparing HLA frequency. At the start point of follow-up, 187 patients (87.8%) had unilateral and 26 patients (12.2%) had bilateral breast cancer. After a 10-year follow-up, 183 patients (85.9%) were unilateral and 30 patients (14.1%) were bilateral. Haplotype frequency of A24-Cw7 was significantly higher in bilateral breast cancer patients compared with unilateral breast cancer patients (p < 0.001). After the 10-year follow-up, 4 of 187 patients (2.1%) with unilateral breast cancer developed bilateral breast cancer. Two of 19 patients (10.5%) with haplotype A24-Cw7 developed bilateral breast cancer, whereas only 2 of 168 patients (1.2%) without haplotype A24-Cw7 developed bilateral breast cancer (p < 0.01). The true frequency of developing contralateral breast cancer in patients with haplotype A24-Cw7 was 93 per 100,000 per year. The risk of bilateral breast cancer in patients with haplotype A24 and Cw7 is 12 times higher compared with those without the haplotype. HLA typing is useful for selecting patients who are at high risk of contralateral breast cancer.

Evolving Concepts in the Management of Lobular Neoplasia

Lobular neoplasia broadly defines the spectrum of changes within the lobule, ranging from atypical lobular hyperplasia (ALH) to lobular carcinoma in situ (LCIS). This continuum of lesions is associated with an increased risk for developing subsequent invasive breast cancer, with the magnitude of that risk corresponding to the degree of proliferative change. The associated risk for developing invasive breast cancer after a diagnosis of lobular neoplasia is multicentric, bilateral, and equal in both breasts. Lobular neoplasia itself may transform into invasive carcinoma, although the frequency of this occurrence is unknown. Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition.

Simultaneous bilateral breast carcinoma: Histopathological characteristics and CD44/catenin-cadherin profile.

Family history of breast carcinoma, multicentric tumor foci in one breast, and in situ lobular carcinoma increase the risk of bilateral breast cancer (BBC), synchronous or metachronous. Synchronous tumors are designated as simultaneous breast carcinoma if they appear at the same time. The CD44 family and cadherin/catenin immunophenotype of this group of BBCs has not yet been evaluated. The aim of this study was to compare clinicopathological characteristics and immunohistochemical profiles of simultaneous BBC and corresponding lymph node metastases in eight patients. In toto 15 primary and 9 metastatic tumors were evaluated. The expression of CD44 variant isoforms, beta-catenin, E, P and N-cadherin were evaluated by immunohistochemistry. Rare types of breast carcinoma were frequent in this group of patients. There were 6 pleomorphic lobular, 5 invasive ductal of usual type, 3 atypical medullary carcinomas, 2 mucinous and one invasive micropapillary carcinoma. The expression CD44v6 was most frequent, followed by CD44v3-10, CD44v5, and CD44v3. CD44v4 was generally not expressed. E-cadherin was expressed in 80% primary tumors, 40% expressed N-cadherin, and 66% expressed P-cadherin. Generally, simultaneous carcinomas had different morphology and different immunophenotype. Each primary tumor was more similar to its corresponding metastatic tumor than to the contralateral primary tumor.

Genetic implications of bilateral breast cancer: a population based cohort study

Women with breast cancer are at high risk of bilateral breast cancer. We aimed to assess the incidence of bilateral breast cancer in relation to age and time since diagnosis of first cancer. We analysed a population-based cohort of 123757 women with a first primary breast cancer diagnosed in Sweden from 1970 to 2000 for frequency of bilateral breast cancers and deaths by means of record linkage. Second primary breast cancers were categorised as synchronous bilateral breast cancers if diagnosed within 3 months of the first primary cancer or as metachronous if diagnosed more than 3 months after diagnosis of first primary cancer. We identified 6550 women who had developed bilateral breast cancer. Age-incidence patterns of synchronous and unilateral breast cancer were similar, although the absolute rates of synchronous bilateral cancer were 50-100 times lower than those of unilateral cancer. A woman aged 80 years or older is at least twice as likely to be diagnosed with synchronous bilateral breast cancer than is a woman younger than 40 years. In the first 20 years after diagnosis of primary breast cancer, incidence of metachronous bilateral cancer decreased from about 800 per 10(5) person-years to 400 per 10(5) person-years in patients diagnosed with primary breast cancer before the age of 45 years, whereas incidence remained at 500-600 per 10(5) person-years in those age 45 years or older at diagnosis. After 30 years' follow-up, cumulative risk of metachronous bilateral breast cancer was about 15% irrespective of age at first primary breast cancer. The higher than expected risk of synchronous bilateral breast cancer could be explained by non-genetic factors. By contrast, incidence of metachronous bilateral cancer fits neither a model of highly penetrant genes nor aggregation of environmental risk factors.

BRCA1/2 mutations as prognostic factors in bilateral breast cancer (BC) patients

9647 Background: Incidence of primary bilateral BC is rare and not extending 5%. BRCA1/2 mutation carriers diagnosed with BC have a strong life time risk of developing a contralateral BC (53% vs 2%). Methods: We analyzed the group of 108 patients with bilateral BC who attended our Cancer Center between 2000 and 2002 and who gave their consent for genetic test. Patients with synchronous BC were defined as having contralateral BC within 1 year. Similarities and differences between BRCA1/2 carriers and non carriers were analyzed in terms of family history, pathology of tumor, age of diagnosis and development of contralateral BC and second cancer. Results: The median age of the group at the time of diagnosis of BC was 47 years (28–76). Before age of 50, BC developed 73% of patients, including 22% before age of 40. Synchronous BC was diagnosed in 30 (28%) patients, metachronous in 78 (72%). Family history of BC was present in 32/108 patients, and of ovarian cancer in 5/108 patients. BRCA1/2 mutation was detected in 32/108 patients. Family history of BC was identified in 46,9% of these patients, comparing to 22,4% of non carriers (p<0.05). Synchronous BC was diagnosed significantly rarer 4/32 (12.5%) in BRCA1/2 carriers than in non carriers group 26/76 (34.2%). Also patients with BRCA mutations when diagnosed were younger than non carriers (41.3 vs 47.9) and time to diagnosis of contralateral BC was shorter. BRCA1/2 carriers had significantly higher incidence of medullary BC (13.6% vs 1.7%). There was no difference in the incidence of other tumor pathology. BRCA1/2 carriers developed significantly more frequent ovarian cancer than non carriers 12/32 and 1/72 respectively. Conclusions: Patients with bilateral BC having BRCA mutations are significantly younger, than non carriers and time of developing of contralateral BC is shorter.They have significantly more frequent family history of BC and higher risk of developing of ovarian cancer. The differences in clinical aspects of BRCA carriers with bilateral BC, should be considered in clinical management. No significant financial relationships to disclose.

Breast cancer risk among the survivors of atomic bomb and patients exposed to therapeutic ionising radiation

Radiation induced breast cancer is a highly complex phenomenon, which most likely involves the accumulation of several genetic and epigenetic events. Studies of atomic bomb survivors, patients who underwent multiple fluoroscopic examinations during treatment for pulmonary tuberculosis, those who received therapeutic radiation for benign breast disease, such as acute post-partum mastitis, or those with an enlarged thymus or skin haemangioma and patients with Hodgkin's disease treated by mantle radiotherapy established that the risk of breast cancer increases with exposure to ionising radiation. The carcinogenic effect of therapeutic or accidental radiation is highest when exposure occurs during childhood and exposure after age 40 imparts low or minimal risk. The risk of bilateral breast cancer is not significantly increased in the survivors of atomic bomb and therapeutic radiations. Fractionated exposures for therapeutic radiation are similar to a single exposure of the same total dose in their ability to induce breast cancer; this risk remains high for many years after exposure. Younger age at first full term pregnancy confers a protective effect against the risk of breast cancer in the survivors of atomic bomb but long-term data on this beneficial effect after therapeutic radiation is not available.

Radiation-induced chromatid breaks as a predictor of breast cancer risk

Purpose: In in vivo models, radiation-induced genomic instability correlates with the risk of breast cancer development. In addition, homozygous mutations in tumor suppressor genes associated with breast cancer development adversely affects the processing and repair of radiation-induced DNA damage. We performed a case-control study to determine whether an assay measuring radiation-induced chromatid breaks correlated with the risk of having bilateral breast cancer. Methods and Materials: Patients were prospectively studied on an institutional review board-approved protocol. We included only women with bilateral breast cancer as cases to obtain patients with a presumed genetic susceptibility for breast cancer. Controls were healthy women without a previous cancer history. A mutagen sensitivity assay using γ-radiation was performed on lymphocytes obtained from 26 cases and 18 controls. One milliliter of whole blood was cultured with 9 mL of blood medium for 91 h and then treated with 125 cGy using a Cs-137 irradiator. Following an additional 4 h in culture, cells were treated with Colcemid for 1 h to arrest cells in metaphase. The number of chromatid breaks per cell was counted using a minimum of 50 metaphase spreads for each sample. Results: Cases had a statistically higher number of γ-radiation-induced chromatid breaks per cell than controls, with mean values of 0.61 ± 0.24 vs. 0.45 ± 0.14, respectively ( p = 0.034, Wilcoxon rank sum test). Using the 75th percentile value in the control group as a definition of radiation sensitivity, the radiation-sensitive individuals had a 2.83-fold increased odds ratio for breast cancer development compared with individuals who were not radiation sensitive (95% confidence intervals of 0.83 and 9.67). Conclusions: These preliminary data suggest that sensitivity to radiation-induced chromatid breaks in lymphocytes correlates with the risk of bilateral breast cancer. Although the differences between cases and controls were statistically significant, the small sample size necessitates that this finding be validated in a larger study. More data are also needed to determine whether this sensitivity is limited to breast cancer patients with a genetic susceptibility for the disease or also applies to the general breast cancer population.

Risk factors for contralateral breast cancer in Chennai (Madras), India.

This is the first cohort study conducted in India to identify risk factors for contralateral breast cancer (CBC) among patients with first primary breast cancer. Patients with first primary breast cancer diagnosed in 1960-1989 at the Cancer Institute (WIA) in Chennai, India, were followed-up until 31 December 1994. The risk of CBC was assessed among unilateral breast cancer (UBC) patients who survived for >12 months following the diagnosis of breast cancer and did not develop a second cancer (n = 2665) and among those who developed a CBC > or =12 months after the diagnosis of breast cancer (n = 39). The age-adjusted incidence of CBC among women with UBC was seven times the incidence (per single breast) in the general population. Among women with UBC the relative risk (RR) was 4.5 (95% CI: 1.1-19.6) comparing those with and without a history of breast cancer in the mother, and 2.8 (95% CI: 1.2-6.7) comparing age at first birth 21-25 versus earlier. The RR was 0.3 (95% CI: 0.1-0.6) comparing those with and without hormone therapy for their UBC. Radiotherapy for the UBC had no significant effect on the incidence of CBC. Positive family history of breast cancer and later age at first childbirth emerged as stronger risk factors for CBC than UBC. Hormone therapy reduces the risk of CBC.

A case-control study of reproductive variables, alcohol, and smoking in premenopausal bilateral breast cancer.

Premenopausal bilateral breast cancer is characterized by a strong family risk, and, consequently, a high probability that inherited susceptibility genes may be segregating in these families. Determining whether risk factors that affect other breast cancer cases have a similar effect in the etiology of bilateral breast cancer is of interest. Therefore, as part of an ongoing genetic-epidemiologic study of premenopausal bilateral breast cancer, we conducted a case-control analysis of reproductive variables, benign breast disease, alcohol, and smoking. Cases had premenopausal bilateral breast cancer, and their unaffected sisters served as controls. A set of reproductive variables--including earlier age at menarche, nulliparity, and late age at first full term pregnancy--appeared to increase the risk of breast cancer; the corresponding confidence limits, however, were wide and straddled the null. In addition, other variables associated with increased premenopausal bilateral breast cancer risk were: use of oral contraceptives, history of benign breast disease, and high alcohol consumption. We found no positive association for smoking. Nulliparity and late age at first full-term pregnancy appeared to have different effects in women with family histories of breast cancer than in women without such a history. We detected no substantial effect modification for the other risk factors. In general, risk factors previously identified for breast cancer (usually postmenopausal, unilateral cases) appear also to increase the risk for premenopausal, bilateral breast cancer.

Risk factors of multiple primary cancers in breast cancer patients.

To clarify risk factors of multiple primary cancers in breast cancer patients, a case-control analysis based on data from medical records was conducted at the Aichi Cancer Center Hospital. For each of a total of 115 multiple primary cancer patients affected by one or two other primary cancers after or concurrently with breast cancer, two patients with unilateral breast cancer were selected as controls by matching age, time of the operation for breast cancer, and survival period. Multiple primary cancer patients were then divided into two groups, 61 cases of bilateral breast cancer and 56 cases of other multiple primary cancers. Conditional multiple logistic regression analysis indicated that relatively heavy smoking (more than 10 cigarettes per day) decreased the risk of multiple primary cancers taken overall (relative risk (RR) = 0.23); overweight status elevated the risk of bilateral breast cancer (RR = 3.01); and greater than average height (RR = 2.20), history of gallstone or cholecystitis (RR = 6.29), and late first birth or nulliparous status (RR = 6.85) elevated the risk of other multiple primary cancers. The effects of weight and height were predominant in the postmenopausal women. As to family history, we could not obtain clear results, though history of cancer among siblings tended to increase the risk of multiple primary cancers (P less than 0.10) and family history of breast cancer was more frequent in patients with bilateral breast cancer (not significant).