Prospective surveillance of women with a family history of breast cancer: auditing the risk threshold

To evaluate current guidelines criteria for inclusion of women in special 'breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at 'less than 'moderate' familial risk'. The Scottish Cancer Registry was then interrogated to determine subsequent age-specific incidence of breast cancer in this cohort and corresponding Scottish population figures. Among 2074 women, with an average follow-up of 4.0 years, 28 invasive breast cancers were recorded up to December 2003, where 14.4 were expected, a relative risk (RR) of 1.94. Eleven further breast cancers were recorded between January 2004 and February 2006 (ascertainment incomplete for this period). The overall RR for women in the study cohort exceeded the accepted 'cutoff' level (RR=1.7) for provision of special counselling and surveillance. The highest RR was found for the age group 45-59 years and this group also generated the majority of breast cancers. The National Institute for Clinical Excellence ('NICE') guidelines appear to be more accurate than those of the Scottish Intercollegiate Guidelines Network ('SIGN') in defining 'moderate' familial risk, and longer follow-up of this cohort could generate an evidence base for further modification of familial breast cancer services.     

Bilateral breast carcinoma: prospective evaluation of factors assisting diagnosis

Bilateral primary breast cancers occur commonly enough to justify adoption of special pre- and post-initial therapy screening. A 13.2% incidence of bilateral breast carcinoma has been found in the breast cancer patients who presented to the Fox Chase Cancer Center with an operatively manageable primary in an arbitrarily defined 30-month period and who have been followed for at least 20 months thereafter. Of the 287 patients seen in those 30 months, 4.5% had synchronously detectable lesions. Xeroradiography is helpful in the initial and follow-up evaluation of the patient for detection of a second primary and may lead to the discovery of an earlier-stage lesion. A history of a family member having a breast cancer was shown to be significant, 26% and 24% for primary and secondary relatives, respectively, and warrant a special screening strategy. Recognition of these factors may lead to earlier detection of curable breast cancers.     

Racial and age differences in multiple primary cancers after breast cancer: A population-based analysis

Summary The occurrence of multiple primary cancers was evaluated among 17,944 white and black female residents of Metropolitan Detroit diagnosed with breast cancer between 1973 and 1983. Invasive second primary cancers were diagnosed among 1106 of these women, almost twice the expected number. Subsequentin situ cancers were detected four times more often than expected. Fifty-six percent of the subsequent invasive cancers were of the breast (Standardized Incidence Ratio, SIR = 3.80). Black women experienced higher risk of subsequent breast cancers (SIR = 5.30) than white women (SIR = 3.62). Highest risk was seen among women first diagnosed before age 40 (SIR for black women = 26.15, SIR for white women = 10.87) and within five years of initial diagnosis. These findings suggest that young breast cancer patients, especially black women, are at high risk of developing a second primary breast cancer soon after their initial diagnosis and should be under continued medical surveillance. The occurrence of multiple primary breast cancers among young women suggests a genetic component to risk. Identification of this subpopulation would be useful in the study of molecular and genetic markers for cancer. Subsequent colon (SIR = 1.24) and cervical (SIR = 1.54) cancers also were diagnosed significantly more often than expected, as were ovarian cancers among white women (SIR = 1.45). These findings are consistent with common etiologic factors associated with these cancers.     

Familial association of histology specific breast cancers with cancers at other sites

Breast cancer histologies show important differences in their incidence pattern, method of detection and management. Aggregation of breast cancer occurs also in families diagnosed for cancer at sites different from the breast. Therefore, the familial association of histology specific breast cancers with cancers at other sites is of great interest. The nationwide Swedish Family-Cancer Database was used to calculate standardised incidence ratios (SIRs) for breast cancer when parents or sibling were diagnosed with cancer at the most common sites. Significant SIRs were found when parents had breast, ovarian, laryngeal, endometrial, prostate, lung and colon cancers. If women were diagnosed before the age of 50 years, the SIRs were significant when parents were diagnosed with breast, ovarian, and prostate cancers, and leukaemia, and when siblings were diagnosed with squamous cell skin, pancreatic, breast and endometrial cancers. If mothers were diagnosed with breast cancer, histology-specific SIRs were ranked as comedo > tubular > ductal > lobular; SIR for medullary carcinoma was not significant but it was high when mothers presented with ovarian cancer. Other associations were between the upper aerodigestive tract and lobular, colon and comedo, larynx and ductal cancer. Moreover, cervical cancer was associated with comedo and endometrial cancer with the medullary histology. In conclusion, histology-specific breast cancers were associated with specific cancer sites and the strength of the association varied among histologies.     

A case of familial breast cancer

The occurrence of breast cancer in 5 members of a family is reported. No specificity of the location, staging or histological typing of the lesions was observed in these cancers. But the characteristics of "hereditary breast cancer", early onset and the occurrence of metachronous double cancers, were observed. As for heredity, it is suspected to be autosomal dominant trait; on the other hand it is more appropriate to assume a poly genic pattern. Recognizing the importance of familial cancer occurrence, it may be possible to detect early cancerous lesions in family members.     

Multiple primary cancers of the colon, breast and skin (melanoma) as models for polygenic cancers

To assess the role of family history in the development of multiple primary cancer, the Swedish Family-Cancer Database was used to analyze second primary cancer in patients born in 1935 to 1996 with an initial primary cancer of the colon, breast and skin (melanoma) by familial cancer in first-degree relatives. Standardized incidence ratios (SIRs) were calculated from site-, sex- and age-specific rates for all persons (offspring) born in 1935 to 1996. Familial risk (SIR) was calculated for the first and second primary cancers in offspring. A Poisson regression analysis was also performed to assess the risk factors for occurrence of second primary cancer. The familial proportion of multiple primary cancers was 29.0% (9/31) for colon, 16.3% (122/747) for female breast and 14.5% (17/117) for melanoma. Compared with all offspring, patients with family history were at a much higher and significantly increased risk for subsequent primary cancer at colon (SIR = 59.1), skin (SIR = 48.2) and female breast (SIR = 7.9). The corresponding SIRs in patients without family history were 13.8, 10.5 and 5.2 at the three sites. The ratios for incidence of second primary to first primary were highest when diagnosis age was less than 40 years. A Poisson regression analysis showed that family history was one of the major risk factors for occurrence of multiple primary cancers at colon, breast and skin. The high risk of second cancer, even in the absence of family history, would be consistent with a polygenic model of carcinogenesis.     

Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia

Epidemiological studies have consistently shown elevated rates of breast cancer among female blood relatives of patients with ataxia telangiectasia (AT), a rare autosomal recessive disease. A large proportion of the members of AT families are carriers of AT-causing gene mutations in ATM (Ataxia Telangiectasia Mutated), and it has been hypothesised that these otherwise healthy carriers are predisposed to breast cancer. This is an extended and enlarged follow-up study of cancer incidence in blood relatives of 75 patients with verified AT in 66 Nordic families. Blood relatives were identified through population registry linkages, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. The ATM mutation carrier probabilities of relatives were assigned from the combined information on location in family, consanguinity, if any, and supplementary carrier screening in some families. Among the 1445 blood relatives of AT patients, 225 cancers were observed, with 170.4 expected, yielding a standardised incidence ratio (SIR) of 1.3 (95% confidence interval (CI), 1.1-1.4). Invasive breast cancer occurred in 34 female relatives (SIR, 1.7; 95% CI, 1.2-2.4) and was diagnosed in 21 women before the age of 55 years (SIR, 2.9; 95% CI, 1.8-4.5), including seven mothers of probands (SIR, 8.1; 95% CI, 3.3-17). When the group of mothers was excluded, no clear relationship was observed between the allocated mutation carrier probability of each family member and the extent of breast cancer risk. We concluded that the increased risk for female breast cancer seen in 66 Nordic AT families appeared to be restricted to women under the age of 55 years and was due mainly to a very high risk in the group of mothers. The findings of breast cancer risk in mothers, but not other likely mutation carriers, in this and other studies raises questions about the hypothesis of a simple causal relationship with ATM heterozygosity.     

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.     

Family History Attributes and Risk Factors for Breast Cancer in Turkey

Background: When dealing with breast cancer, early detection is closely associated with determining andclosely monitoring high risk groups. The aim of this study was to determine the preventable risk factors thatare specific for our country, and to understand which risk factors were most predominant. Materials andMethods: The study was planned as a case-control design. Women diagnosed with breast cancer who visitedthe Surgery, Obstetrics and Gynaecology, and Radiation Oncology outpatient clinics of the Izmir Dokuz EylulUniversity (DEU) School of Medicine were accepted as the case group. Then a control group matched for agewas established among females who visited the outpatient clinics on the same days. A questionnaire preparedby the researchers was implemented using a face-to-face interview technique. The Mann-Whitney U test wasused in the comparisons of the group averages, and the Pearson chi-square test in the comparisons betweengroups. In order to determine the dominant risk factors, binary logistical regression test was implemented.Results: A total of 138 patients, 69 cases and 69 controls, were included in the study. A significant difference canbe detected between the groups in terms of BMI, smoking, breast cancer prevalence among first degree familymembers, presence of breast cancer among distant family members, existence of other types of cancers amongfamily members and the age of onset of menopause (p<0.05). Logistical regression analysis revealed that thepresence of breast cancer among first degree relatives increased the risk of developing breast cancer 5.7 times.Conclusions: Although some results of this study are compatible with findings in the literature, some are not. Inorder to determine unique risk factors, there is a clear need for large-scale studies.     

Surveillance of women at increased risk of breast cancer using mammography and clinical breast examination: further evidence of benefit

Women with a significant family history of breast cancer are generally offered early surveillance by mammography and often clinical breast examination (CBE). The evidence base for surveillance has been questioned. We reviewed its effectiveness in terms of tumour size, lymph node status and survival in 7,475 women seen over a 22-year period in the Manchester Family History Clinic. We diagnosed 139 invasive and 26 in situ breast cancers. Seventy-six percent of the invasive cancers were screen detected, 65% node negative and 71% <2 cm in diameter at diagnosis. Twenty-one tumours were BRCA1 positive and were significantly more likely to be grade 3, ER/PR negative (p < 0.0001) and have a poorer survival. CBE contributed to 30% of cancer diagnoses and was responsible for discovery of nine mammographically occult tumours. The cost per quality life year was estimated at ￡13,080 for tumours detected by CBE and not by mammography. We conclude that screening by annual mammography and CBE between age 35-50 years and 18 monthly from 50 to 60 years may diagnose breast cancer in a less advanced state in terms of size and node status compared with symptomatic cancers and, apart from BRCA1 carriers, is likely to contribute to improved long-term outcome compared with no surveillance.     

Psychological distress in women at risk for hereditary breast cancer: the role of family communication and perceived social support

Background: Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at‐risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. Objective: To examine the associations of family communication and social support with long‐term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. Methods: The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer‐related family communication, perceived social support, and demographics were assessed. Results: Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer‐specific distress through open communication within the family. Discussion: These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long‐term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.     

Breast cancer family history as a risk factor for early onset breast cancer

Summary Since full breast cancer screening is not generally recommended for young women, it is important to identify individuals who are at higher risk for early onset breast cancer. We investigated the relationship between age of onset of breast cancer in 328 probands (consecutively ascertained patients from our oncology clinic) and breast cancer incidence and age of onset in their female relatives. We found that a family history of early onset breast cancer was associated with higher risk of early onset breast cancer. A family history of early onset breast cancer occurred more frequently among young (<40) breast cancer probands than among older (40) breast cancer probands (p<0.001; OR = 23). This relationship was particularly evident when the analysis was restricted to thehereditary breast cancer probands (p<0.001; OR = 44). We also observed a positive family history of breast cancer (any age) more frequently in young breast cancer probands than in older breast cancer probands (p<0.001; OR = 2.8). These observations have important pragmatic implications for surveillance. We recommend intense surveillance for breast cancer, initiated earlier, for women with close relatives diagnosed with early onset breast cancer.     

Familial effects of prostate and other cancers on lifetime breast cancer risk

Summary Lifetime probabilities of developing breast cancer were calculated for first-degree female relatives of three groups of breast cancer patients: 114 with bilateral cancer, 186 unselected, and 88 males. The patients were classified according to whether they had a family history of prostate, endometrial, or ovarian cancer, or no family history of these cancers. In families of unselected female and male patients with no family history of prostate, endometrial, or ovarian cancer, the lifetime probability of developing breast cancer was 11.4%. The risk increased slightly to 13.5% when these other cancers may or may not have present (i.e., they were ignored, which is the usual method in computing risks) and increased further to 25.5% when prostate, endometrial, or ovarian cancer was present in the family. In families of patients with bilateral cancer the respective risks were 10.9%, 17.3%, and 34.4%. A family history of prostate cancer increased lifetime risk consistently in each of the groups, to 29.0% in the unselected and male groups and to 38.2% in the bilateral group. Endometrial cancer increased risk only in the bilateral group (to 41.8%) as did ovarian cancer (to 54.6%). Increased risk of breast cancer with a family history of endometrial or ovarian cancer appeared to be influenced by families with hereditary breast-ovarian cancer or the cancer family syndrome. The results indicate that prostate cancer, and endometrial and ovarian cancers in some families, can significantly increase breast cancer risk and should be taken into account when counseling women about their breast cancer risk.     

Does a Positive Family History Influence the Presentation of Breast Cancer?

Introduction: An important risk factor for developing breast cancer is a positive family history of breast cancer. In Malaysia, there is no population-based breast screening programme, but the clinical practice guidelines suggest increased surveillance for those with a positive family history ie mammography for those 40 years old and above, breast self-examination and clinical breast examination yearly. Objective: To determine if women with a family history of breast cancer present with earlier stages of disease.Methodology: From Jan 2001 to Dec 2006, 1553 women with breast cancer presenting to the University Malaya, where family history was recorded, were eligible for this study. Women with a first or second degree relative with breast cancer were compared with those who have no family history with regard to their race, age, stage, size and duration of symptoms. The Chi Square test of significance was used for analysis. Results: Out of 1553 patients, 252 (16.2%) were found to have a relative with breast cancer out of which 174 (11.2%) had at least one affected first degree relative. There were no significant difference in the incidence of positive family history between the Malays, Chinese and Indians. 20% below the age of 40 years old had a positive family history compared with 12.6% in women with no family history. (p<0.05). There was no significant difference in stage at diagnosis between those with and without family history, ie 24.2% late stages (Stage 3 and 4) in the group with no family history compared with 21.8% in the group with family history. (p>0.05). The mean size in the group with no family history was 4.4 cm compared to 4.1 cm in the group with family history. There was a significant difference in screen-detected cancers in the women with family history, 10.7% compared with 5.1% of screen-detected cancers in the group without a family history. However there was no difference in the duration of symptoms between the 2 groups - 25.8% in the women without a family history presented after 1 year of symptoms compared with 22.4% in the group with a family history (p>0.05). Conclusion: Having a family history of breast cancer does not appear to have much impact on the health-seeking behavior of women. Even though there were more screen detected cancers, these comprised only 10% of the group with family history. Public education should target women at risk ie with family history to encourage these women to present earlier and to undergo screening for breast cancer.     

Incidence of multiple primary cancers in a cohort of women diagnosed with breast cancer in southeast England

Among women in the Thames Cancer Registry database with a first breast cancer diagnosed between 1961-1995 observed numbers of subsequent cancers were compared with expected numbers and standardized incidence ratios were calculated. The occurrence of breast cancers subsequent to cancers at other sites was also examined. Women diagnosed with breast cancer before age 50 had significantly elevated risks for 9 cancer sites namely, oesophagus, stomach, lung, bone, connective tissue, breast, corpus uteri, ovary and myeloid leukaemia compared with 2 sites (corpus uteri and myeloid leukaemia) in women diagnosed at age 50 and above. Some of these associations are consistent with the effects of known inherited cancer susceptibility genes, shared environmental factors, or therapy.     

First experiences in screening women at high risk for breast cancer with MR imaging

Women with a genetic predisposition for breast cancer are often advised surveillance with physical examination twice a year and mammography once a year from 25 years onwards. However, the sensitivity of the mammography decreases when breast tissue is dense and this is seen in 40–50% of women under 50 years. We therefore investigated whether magnetic resonance imaging (MRI) in addition to the normal surveillance could detect cancers otherwise missed. In 109 women with over 25% risk of breast cancer, MRI was performed because over 50% dense breast tissue was seen at mammography and no suspect lesion was seen at the previous screening. MRI detected breast cancers in three patients (2.8%) occult at mammography and with no new palpable tumor, twice at stage T1bN0 and T1cN0 once. Two cancers were expected. MRI was false positive in six women, resulting in two benign local excisions because ultrasound or fine needle examination confirmed suspicion. We had no false negative MRI results. MRI proved true benign in four BRCA 1/2 gene mutation carriers at histologic examination. Preoperative wire localization of the malignancies detected at MRI proved necessary as the tumor was not palpable in the lumpectomy specimen nor visible at specimen radiology. The extra cost of breast MRI in addition to mammography and physical examination was uro13.930 per detected cancer. The cost of the detection of one breast cancer patient in our national screening program is uro9000. During follow-up of patients with a familial risk in whom the first breast cancer was detected at MRI, MRI detected two recurrent cancers in stage T1bN0 and T1cN0 and one contralateral cancer T1aNo. Breast MRI is promising in screening young women at high risk for breast cancer, as it can advance the detection of cancers still occult at mammography and physical examination; but the cost may be considerable.     

Patterns of changing cancer risks with time since diagnosis of a sibling

Family history is a well‐known risk factor for many cancers. However, it is important to know if/how the familial risk of cancer changes over time. For each of four major cancers (colorectal, breast, prostate and melanoma), we identified siblings of cancer patients (case siblings) and siblings of matched cancer‐free controls sampled from Swedish population‐based registers. Effects of age and time since diagnosis on sibling risks were examined using Poisson regression and presented graphically as smoothed hazard ratios (HRs). Screening effects were investigated by comparing hazards before/after the introduction of mammography for breast cancer and prostate‐specific antigen (PSA) testing for prostate cancer. Case siblings had higher cancer incidence than control siblings for all cancers at all ages, with overall incidence rate ratios (IRRs) of 2.41 (95% confidence interval 2.14–2.71) for colorectal cancer, 2.37 (2.24–2.52) for breast cancer, 3.69 (3.46–3.93) for prostate cancer and 3.20 (2.72–3.76) for melanoma. Risks were highest in siblings who were young when the first cancer was diagnosed in the family, with siblings aged 30–40 having IRR 9.05 (3.03–27.00) for colorectal cancer and 4.30 (2.87–6.45) for breast cancer. Smoothed HRs remained fairly constant for up to 20 years except for prostate cancer, where the HR decreased steeply during the first few years. After introduction of PSA testing, men had higher incidence of prostate cancer shortly after diagnosis in a brother, but no such screening effect was found for breast cancer. Our findings can help inform the screening and counseling of family members of cancer patients.     

Age of onset in familial breast cancer as background data for medical surveillance

Background:

Familial breast cancers are known to be of early onset. This article provides differences in the age of onset of breast cancer and death by breast cancer between women with and without a family history.

Methods:

The Swedish Family-Cancer Database was used to estimate the cumulative risk of breast cancer and death by breast cancer according to family history with a stratified Cox model. Family history was defined separately for affected mother or sister considering their diagnostic ages.

Results:

The age to reach the same cumulative incidence as women without family history decreased with decreasing diagnostic age of the affected relative. Women with a maternal history reached the risk of women lacking a family history at the age of 50 years between 12.3 (mother affected <40 years) and 3.3 years (mother affected >82 years) earlier. The trend for breast cancer mortality was essentially similar.

Conclusions:

Women with mother or sister affected by breast cancer are diagnosed and die at earlier ages than do women without family history. The differences depend on the diagnostic age of the affected relative. The present data may provide a rationale to derive recommendations for the starting age of screening in women with affected family members.     

数据挖掘分析MYB家族在乳腺癌中的表达及其预后评估价值

目的：通过数据挖掘分析MYB家族（包括MYB、MYBL1和MYBL2）在乳腺癌中的表达和预后评估价值。方法：利用Oncomine、GEPIA2、cBioPortal、bc-GenExMiner v4.4、Kaplan-Meier Plotter和DAVID数据库分析MYB家族基因在乳腺癌中的表达、变异、临床病理特征相关性、预后意义,并进行功能富集分析。结果：MYB家族在多个数据集中显示其在乳腺癌组织的表达高于正常乳腺组织（P < 0.05）。在乳腺癌中,MYB家族基因主要以基因扩增、mRNA转录增强和转录减弱的方式变异。MYB家族基因表达与乳腺癌患者年龄、分子分型、SBR分级等临床病理特征相关（P < 0.01）。其中,在三阴性乳腺癌、基底细胞样乳腺癌和P53突变型乳腺癌中,MYB低表达、MYBL1和MYBL2高表达（P < 0.01）。MYB低表达和MYBL2高表达的乳腺癌患者无复发生存期和进展后生存期缩短（P < 0.01）。单因素Cox分析结果显示,MYB低表达和MYBL2高表达的转移复发乳腺癌患者预后差（P < 0.01）。多因素Cox分析结果表明MYBL2可作为乳腺癌转移复发的独立预后因子（P < 0.05）。同时,MYBL2共表达基因主要富集于细胞分裂生物学过程和细胞周期信号通路。结论：MYB家族成员在乳腺癌转移复发过程中发挥重要作用,可作为潜在的临床诊断和预后评价标志物,为后续深入开展分子机制研究和药物开发提供了依据和方向。