Familial bilateral breast cancer

The occurrence of bilateral breast cancers in three members of one family is reported. In two members, evidence of a distinct primary lesion in each breast was verified. The occurrence of unilateral breast cancer and other cancers in other members of the family was surveyed. Recommendations for early detection and surveillance in familial breast cancer at the present time should be by aggressive and close follow-up of the affected members. Absence of reliable markers preclude effective surveillance for early detection or susceptibility.     

Family history of breast cancer,age and benign breast disease

A major risk factor for breast cancer is having a first-degree family history of the disease. Benign breast disease (BBD), particularly atypical hyperplasia, is also associated with an increased risk of breast cancer. However, the relationship between family history of breast cancer and BBD is unclear. From 1989 through 1997, 80,995 participants in the Nurses' Health Study II were followed; 16,849 reported a first diagnosis of BBD. Pathology slides were reviewed for 1,465 women who reported having a tissue biopsy, and these were classified as nonproliferative BBD, proliferative BBD without atypia or atypical hyperplasia. Women with a family history of breast cancer were more likely to report a physician diagnosis of BBD [rate ratio (RR) = 1.38, 95% confidence interval (CI) 1.29-1.46]. The magnitude of this association declined with age from RR = 1.96 (95% CI 1.55-2.47) at 25-29 years to RR = 1.20 (95% CI 0.95-1.52) at age 45-50 years. Among women with proliferative disease, those with a family history of breast cancer were almost 3 times as likely to have atypia (prevalence odds ratio = 2.72, 95% CI 1.23-5.89) than those with no family history. In conclusion, women with a family history of breast cancer appear to be at increased risk of being diagnosed with BBD, in particular the high-risk types of BBD associated with a greatly increased risk of breast cancer. This link adds weight to the belief that BBD with atypia is a precursor or marker lesion for breast cancer.     

Family history of breast cancer and short-term effects of childbirths on breast cancer risk

The long-term protective effect of a pregnancy on breast cancer risk is preceded by a short-term adverse effect, possibly reflecting a promoting effect of pregnancy hormones. In the present study, we explore whether a family history of breast cancer modifies time-related effects of pregnancies, with special emphasis on the transient increase in risk of breast cancer shortly after birth. Our study cohort comprises 1,067,289 Norwegian women aged 20-74 years. The mean follow-up time was 18 years. Incidence rate ratios were estimated by Poisson regression analyses of person-years at risk. Of the 7,377 women diagnosed with breast cancer during follow-up, a total of 828 (11%) had a mother or a sister with breast cancer diagnosis. Women with a family history of breast cancer had a 2-3-fold higher risk of breast cancer than did women without any affected family member, highest for those with a relative diagnosed before they were 50 years. Similar to women without a familial excess risk, increasing parity was associated with an overall protective effect among women with a familial predisposition, regardless of age at diagnosis of the relative. Whereas women with no familial excess risk experienced a transient increase in risk mainly after late age births, women with a family history of breast cancer experienced an adverse effect of pregnancies also at younger ages. The present results give further support to the hypothesis that the adverse effect of a term birth can be explained by a promoting effect of pregnancy hormones.     

Primary synchronous bilateral breast cancer: Epidemiological approach

Summary Twenty-eight (1.69%) cases of primary synchronous bilateral breast cancer (PSBC) out of 1,654 new cases were studied. PSBC compared with unilateral cases had a significantly higher (p<0.001) first degree family history of breast cancer; high frequency of subareolar location; no predominance of lobular and non-invasive types; no significantly different percentage of pathological stage I presentation. As there is no complete agreement on what constitutes a PSBC, studies should be carried out to fomulate a more precise definition of this entity.     

Family history and breast cancer tumour characteristics in screened women

Women with a family history of breast cancer have an increased risk of the disease. However, since they tend to experience greater surveillance for the disease, their breast cancers may be detected at an earlier stage, thus making it difficult to assess reliably whether tumour characteristics vary by family history. Information on 9,731 Million Women Study participants with screen-detected breast cancer, diagnosed in 1996-2003, and 37,983 matched controls, who also attended routine screening but were not diagnosed with breast cancer, was used to estimate adjusted relative risks (RRs) of screen-detected breast cancer in women with a family history of the disease. Women with a family history of breast cancer had an increased risk of screen-detected breast cancer (RR 1.57; 95% CI:1.47-1.68) compared with those without such a family history. The RRs were 1.58 (1.46-1.71) and 1.55 (1.34-1.80) for invasive and in situ breast cancer; 1.63 (1.49-1.79) and 1.55 (1.32-1.83) for node-negative and node-positive disease; and 1.56 (1.42-1.70), 1.75 (1.39-2.21) and 1.71 (1.28-2.29) for ductal, lobular and tubular cancers. There was no significant difference in the RR of screen-detected breast cancer associated with a family history of the disease according to invasiveness, size, nodal status, malignancy grade or morphological type of the breast cancer.     

The impact of bilateral breast cancer on the prognosis of breast cancer: a comparative study with unilateral breast cancer

BACKGROUND: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We assessed the impact of synchronous and metachronous bilateral breast cancer on the prognosis compared with unilateral breast cancer. METHODS: Between January 1, 1960 and December 31, 2001, 1,214 women were treated for primary operable breast cancers. Thirteen (1.1%) had synchronous bilateral breast cancer; 33 (2.7%) had a metachronous contralateral breast cancer. We compared age at operation, menopausal status, clinical stage, tumor size and histology, lymph node status, hormone receptor status, and use of adjuvant chemotherapy or hormone therapy, and we analyzed the impact of these factors on recurrence and survival in the 46 patients with bilateral breast cancer and the 1,168 patients with unilateral breast cancer. RESULTS: The 5-and 10-year disease-free survival rates, respectively, were 65% and 65% in metachronous cases, 85.7% and 64.3% in synchronous cases, and 77.9% and 72.1% in unilateral cases. There was no significant difference in overall survival among the three groups. On multivariate analysis, metachronous bilaterality, tumor size, lymph node status and adjuvant hormone therapy were each independent risk factors for recurrence, whereas bilaterality of breast cancer did not influence overall survival. CONCLUSIONS: Our data suggest that metachronous bilateral breast cancer is associated with shorter disease-free survival than synchronous bilateral or unilateral breast cancer, although overall survival does not differ among the 3 groups. Patients with metachronous bilateral breast cancer should be followed particularly closely in order to detect recurrence early and maximize quality of life.     

原发性双侧乳腺癌

原发性双侧乳腺癌(PBBC)的总体发病率不高,但近年来有逐渐增高的趋势,所以有必要提高对这一疾病的认识.本文复习国内外的相关文献,系统阐述PBBC的病因、流行病学特点、诊断、治疗,特别是预防等相关问题.根据乳腺两侧的原发病灶间隔期是否超过6个月,将PBBC分为同时性和异时性.对于危险因素各家论述涉及较多,其中基因研究是热点所在,也是目前研究的重点.因为PBBC不是转移癌,它与单侧乳腺癌的愈后没有明显差别,所以一经确诊应该采取积极治疗.对于PBBC的预防方法,各家提出意见不一,其中也存在一些争论.     

Family history and risk of breast cancer in hispanic and non-hispanic women: the New Mexico Women's Health Study

Objectives: Many epidemiologic studies have demonstrated that an increased risk of breast cancer is associated with positive family history of this disease. Little information had been available on the relationship of breast cancer risk with family history in Hispanic women. To investigate the association of family history of breast cancer on the risk of breast cancer, we examined the data from the New Mexico Women's Health Study (NMWHS), a statewide case–control study. Methods: In this study 712 women (332 Hispanics and 380 non-Hispanic whites) with breast cancer and 844 controls (388 Hispanics and 456 non-Hispanic whites) were included. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI), adjusted for sociodemographic, medical, and reproductive factors. Results: We found an increased risk in women with a history of breast cancer in one or more first-degree or second-degree relatives (OR = 1.5, 95% CI 1.2–1.9), first-degree relatives (OR = 1.3, 95% CI 1.0–1.8) and second-degree relatives (OR = 1.6, 95% CI 1.2–2.2). Hispanic women had higher risk estimates for a positive family history (OR = 1.7, 95% CI 1.1–2.5) than non-Hispanic white women (OR = 1.4, 95% CI 1.0–2.0); however, the differences were not statistically significant. In both ethnic groups a higher risk was observed in premenopausal women compared with postmenopausal women and women diagnosed with breast cancer before age 50years compared with older women. Conclusions: The results indicate that Hispanic women with a family history of breast cancer are at increased risk of breast cancer.     

Correlations between family history and cancer characteristics in 2256 breast cancer patients

A comparison of 692 early invasive breast cancer with, and 1564 without, a family history of breast cancer showed that the former were younger at diagnosis (P=0.002), had smaller tumours (P=0.012), were more frequently oestrogen receptor positive (P=0.006) and diagnosed preclinically (P<0.001).     

Family history of breast or ovarian cancer modifies the risk of secondary leukemia after breast cancer: results from a population-based study

We evaluated the impact of a family history of breast/ovarian cancer on the risk of secondary leukemia following breast cancer. At the Geneva cancer registry, we identified 4,397 patients diagnosed with invasive breast cancer between 1990 and 2004. Patients were followed up for leukemia until the end of 2005. Family history was categorized as positive in patients with >or=1 first- or second-degree relative with breast/ovarian cancer. We compared leukemia rates in patients with positive and negative family histories with those expected in the general population, generating standardized incidence ratios (SIRs). With Cox regression analysis, we calculated adjusted risks of secondary leukemia in patients with familial risks compared to those without it. Breast cancer patients had a significantly increased risk of secondary acute leukemia (SIR 3.2, 95% CI: 1.2-6.9) but not of chronic leukemia (SIR 1.6, 95% CI: 0.6-3.5). Among patients with a positive family history (n = 1.125, 25.6%), the SIRs were 5.7 (95% CI: 1.2-16.6) for acute and 5.2 (95% CI: 1.4-13.3) for chronic leukemia. Among breast cancer patients, family history was independently associated with leukemia [adjusted hazard ratio (HR(adj)) of 3.2, 95% CI: 1.1-9.2, among patient with vs. without family history]. The effect of family history was stronger for chronic leukemia (HR(adj): 11.6, 95% CI 1.3-104.7) than for acute leukemia (HR(adj) 1.6, 95% CI: 0.4-6.6). Breast cancer patients with a family history of breast/ovarian have an increased risk of secondary leukemia, both compared to the general population as well as to breast cancer patients without family histories. This excess risk is largely due to the increased risk of secondary chronic leukemia.     

Phenotypic similarities in bilateral breast cancer

Bilateral breast cancers that develop at similar times in an individual are likely to have been subjected to similar hormonal, environmental and genetic influences during tumourogenesis compared with metachronous tumours. As such, it is possible that tumour phenotype in synchronous bilateral breast cancer may display similar biological characteristics. The aim of this study was to identify phenotypic similarities between synchronous and metachronous bilateral breast cancers which may suggest a common origin. Thirty-three cases of synchronous and 46 cases of metachronous bilateral breast cancer that displayed similar tumour type were analysed for concordance in relation to various histological and immunohistochemical parameters. A higher level of concordance was demonstrated for synchronous cases with the highest level seen for oestrogen receptor. It is likely that this is related to similar tumourogenic pathways occurring at equivalent exposure times to various environmental and hormonal influences, although, in a proportion of cases, inherited genetic factors may play a role.     

雌激素受体表达与癌家族史阳性乳腺癌的关系

目的　为了探讨癌家族史阳性乳腺癌妇女ER水平是否高于非癌家族性乳腺癌者。方法　采用莹光组织化学法检测了本院 1985～ 1998年间 430例妇女可手术乳腺癌的新鲜组织ER水平 ,对其中癌家族史阳性乳腺癌ER与非癌家族性乳腺癌ER水平进行比较分析。结果　在 430例乳腺癌组织总的ER阳性率为 5 0 .2 % (2 16 / 430 ) ,其中绝经期前、后ER阳性率分别为 46 .3 % (6 8/ 14 7)和 5 0 .7% (10 7/ 2 11)。癌家族史阳性乳腺癌ER阳性率为 5 5 .1% (2 7/ 49) ;家族性乳腺癌ER阳性率为 72 .2 % (8/ 11) ;非癌家族性乳腺癌ER阳性率为 49.6 % (189/ 381)。结论　癌家族史阳性乳腺癌ER和家族性乳腺癌ER水平分别与非癌家族性乳腺癌ER相比 ,各呈明显增高倾向 ,但经统计学处理P >0 .0 5 ,认为无显著差异。本组乳腺癌病人中至少半数病例属于雌激素受体依赖性肿瘤 ,而且绝经期后水平略高于绝经期前者。     

41例双侧原发性乳腺癌的临床病理特征分析

目的:探讨双侧原发性乳腺癌(bilateral primary breast cancer,BPBC)的临床病理特征.方法:回顾分析41例BPBC与409例单侧乳腺癌(unilateral breast cancer,UBC)的临床病理资料,应用单因素分析,分析BPBC的临床病理特点及其危险因素.结果:BPBC组中第二侧原发乳腺癌中原位癌(ductal carcinoma in situ,DCIS)的比例显著高于第一侧原发乳腺癌(17.1％∶2.4％,P=0.005).BPBC组中一级或二级亲属患乳腺癌的比例显著高于UBC组(24.4％∶6.3％,P=0.001).与UBC相比,BPBC组在发病年龄、肿瘤大小、临床分期、组织学分级、病理类型、分子分型、雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor,PR)、人表皮生长因子受体2(human epidermalgrowth factor receptor-2,HER2)、细胞增殖核抗原Ki67的表达无显著差异.8例同时性BPBC中,4例患者对侧乳腺触诊阴性,通过乳腺钼靶成像发现微小钙化进而诊断为BPBC.结论:乳腺癌家族史是BPBC明确的发病危险因素,乳腺钼靶检查有助于对侧触诊阴性的同时性BP-BC的诊断.     

Disparities in cancer screening in individuals with a family history of breast or colorectal cancer

BACKGROUND:

Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population‐based survey.

METHODS:

By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years.

RESULTS:

The authors found no significant BC screening disparities by race/ethnicity or income in the family history risk groups. Racial/ethnic disparities were more evident in CRC screening, and the Latino‐white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino‐white difference in CRC screening (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11‐0.60) was more substantial than that for individuals with no family history (OR, 0.74; 95% CI, 0.59‐0.92).

CONCLUSIONS:

Knowledge of their family history widened the Latino‐white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino‐white screening disparity in Latinos most susceptible to CRC. Cancer 2011;. © 2011 American Cancer Society.     

114例同时性双乳癌临床及预后的回顾性分析

目的研究原发同时性双侧乳腺癌（以下简称同时性双乳癌）的临床病理、治疗及预后情况。方法回顾性分析中国医学科学院肿瘤医院1999年1月至2013年3月收治的114例同时性双乳癌患者的临床病理资料及随访资料。结果同时性双乳癌第一癌及第二癌病理类型以浸润性导管癌为主,原发灶手术方式以乳腺全切为主,腋窝淋巴结手术方式以清扫术为主。同时性双乳癌第一癌及第二癌激素受体阳性率高达70%,HER2阴性病例的比例（第一癌为60.5%,第二癌为64.0%）明显高于HER2阳性比例（第一癌为20.2%,第二癌为15.8%）。第一癌肿瘤大小、第一癌腋窝淋巴结分期、第一癌及第二癌TNM分期是影响同时性双乳癌预后的独立因素（均P〈0.05）。结论同时性双乳癌总体发病率较低,既往文献报道的手术方式多以改良根治术为主。第一癌的肿瘤大小及腋窝淋巴结分期能够影响患者的预后,分期较早的同时性双乳癌拥有更好的预后。     

Incidence and risk factors associated with bilateral breast cancer in area with early age diagnosis but low incidence of primary breast cancer: analysis of 10-year longitudinal cohort in Taiwan

Summary This study aims to examine the incidence and risk factors of bilateral breast cancer in area with low incidence rate. A total of 120 and 1902 women with bilateral and unilateral breast cancers were enrolled; various factors, including those concerning their medical history and life style, were extracted. Using Kaplan–Meier method, we calculate the cumulative incidence of contralateral breast cancer. The results show as follows. The cumulative incidences of contralateral breast cancer at 1, 3, 5 years after diagnosis of first breast cancer were 1.15, 1.94, and 2.97%, respectively. The statistically significant risk factors included menopause (Hazard Ratio (HR) =1.56, (1.00–2.42)), invasive lobular carcinoma (HR=2.98, (1.35–6.56)), receiving chemotherapy (HR=2.21, (1.43–3.42)) and/or radiotherapy (HR=3.32, (2.19–5.05) and a protective factor was tamoxifen therapy (HR=0.5 (0.34–0.74). Size of the second occurred tumour (2.97 cm) tended to be smaller than the first one (3.58 cm) with borderline statistical significance (p=0.0731). Comparing to the existing data on Western countries, we find a higher risk for developing contralateral breast cancer in Taiwan where a low incidence of first breast cancer rate with early age diagnosis is noted. It suggests that first primary breast tumour with early age of onset and lobular carcinoma are found more likely to develop bilateral breast cancers.Tony Hsiu-Hsi Chen and King-Jen Chang equally contributed to this article.     

Increased risk of pancreatic,thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study

The association between a family history of breast cancer (FHBC) in female first-degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site-specific cancers in men with and without FHBC. A population-based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age-matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow-up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07-1.70), 1.33 (1.12-1.56), 1.28 (1.13-1.44) and 3.03 (1.130-8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11-2.57) and increased the risk of thyroid cancer by 3.41-fold (95% CI: 1.10-10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation-related cancer surveillance.     

Interval breast cancer risk associations with breast density,family history and breast tissue aging

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case–control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69–0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts—an increased risk of developing an interval breast cancer.