Risk of colorectal cancer after breast cancer

doi:10.1016/S0140-6736(00)04197-0

The Lancet

Volume 357, Issue 9259, 17 March 2001, Pages 837-840

https://doi.org/10.1016/S0140-6736(00)04197-0 Get rights and content

Summary

Background

History of breast cancer has been reported as a risk factor for colorectal cancer in women. In view of the ambiguous nature of existing evidence and the growing interest in targeted colorectal cancer prevention, we sought to quantify this risk.

Methods

We used the Surveillance Epidemiology and End Results (SEER) database to estimate risk of colorectal cancer after breast-cancer diagnosis in women with first incident breast cancer between 1974 and 1995. Observed colon and rectal cancer risk was compared with that expected in the general population. We stratified comparisons by age at breast-cancer diagnosis, stage of cancer, ethnic origin of patient, and follow-up time.

Findings

Overall, women with previous breast cancer were 5% less likely (95% CI 1-9) to develop colon and 13% less likely (6-19) to develop rectal cancer than women in the general population. Stratified analyses suggested that the risk reductions observed for colon and rectal cancer were most pronounced for women with breast cancer diagnosed after age 65 years, in white women, women with local stage breast cancer, and women diagnosed in the later study years (1990–94).

Interpretations

Breast cancer does not increase subsequent colorectal cancer risk, and reduced risk was seen for certain subgroups of women. Because no biologically plausible endogenous protective factor has been identified, we suggest that reduced risk could stem from an accumulation of exposures that increase breast-cancer frequency but protect against colorectal cancer.

Introduction

A history of breast cancer continues to be reported as a risk factor for colorectal cancer.1, 2 Supporting evidence, however, seems ambiguous. Two reviews that assessed mostly the same studies, both published in 1994, estimated summary colorectal cancer relative risks of 1·1 and 1·15, respectively, for breast-cancer history. The conclusions of the two were that the risk increase was not large enough to alter colorectal screening practice in women with breast cancer.3, 4 However, clinicians might still perceive a risk greater than the evidence suggests. A clinical expert panel that convened in 1998 concluded that the risk increase associated with breast-cancer history was similar to that conferred by having a first-degree relative with colorectal cancer.⁵ Our aim was to assess data from a large population-based source to find out whether this belief is well founded.

Section snippets

Patients

Eligible women were those diagnosed with a first primary invasive breast cancer (International Classification of Diseases, ninth edition [ICD-9] 174·0-144·9) between 1974 and 1995 and reported to the Surveillance Epidemiology and End Results (SEER) database. At that time, SEER was a network of population-based cancer registries covering nine geographic areas that included about 10% of the US population. This database, maintained by the National Cancer Institute, is the closest approximation to

Results

253 989 eligible women were identified from the SEER database. 1936 were excluded for diagnosis at death or on necropsy only, 3168 for zero follow-up, 12 141 for ethnic origin other than black or white, 232 for age younger than 25 years at diagnosis, and 9347 for unknown cancer stage at diagnosis. 227 165 women were included in the study. Table 1 shows frequency distributions of selected characteristics for the full study cohort, and for women who developed colon and rectal cancer. Median age

Discussion

Our results show that women with breast cancer do not have an excess risk of subsequent colorectal cancer. The data also suggest that some women are at lower risk of colorectal cancer than those in the general population. Mechanisms explaining such risk reductions are, however, only speculative. The risks in the subgroups are consistent with the hypothesis that hormone-replacement therapy offers protection against colorectal cancer. Although stil debated,¹¹ research shows that

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The literature to date has suggested a potential increase in colorectal cancer (CRC) among patients with breast cancer.
We performed a systematic review of the literature and included 37 retrospective cohort studies and 8 case-control studies. The primary aim was to determine the prevalence of CRC. Secondary aims included analysis of adenomatous polyps and analysis of CRC prevalence by age. We calculated pooled prevalence rates and odds ratios (ORs) using random effects models with 95% confidence intervals (CI).
We identified 1,055,917 individuals with breast cancer among whom 9097 cases of CRC were detected. The pooled event rate for CRC was 0.7% (95% CI, 0.6%-0.9%; I²=97%). Four case-control studies reported prevalence of CRC (N=17,873 patients with breast cancer and 70,366 controls), including 46 cases of CRC in the patients with breast cancer, and 272 CRC in the controls (OR, 1.2; 95% CI, 0.4%-3.7%; P = .7). Six studies reported prevalence of advanced adenomas in patients with breast cancer (N=1087) compared with controls (N=1356) with 62 cases of advanced adenomas in patients compared with 47 in the controls (OR, 1.5; 95% CI, 0.97-2.2; P = .07). In patients with breast cancer <50 years old (4 studies, N=64,706), the pooled OR was increased (OR, 2.5; 95% CI, 1.7-3.5; P =.001). In 3 studies of women <45 years old (N=92,594), the risk was increased (OR, 2.3; 95% CI, 1.7-2.6; P < .001).
Patients with breast cancer should not undergo CRC screening at intervals different from the general population. In patients with breast cancer <50 years old, CRC screening should be considered at age 45 years.
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A few studies have examined the risk of colorectal cancer following a diagnosis of breast cancer, but the results are conflicting. In two studies based on SEER data, a small but still significant excess of colon cancer was found, while the risk of rectum cancer was not significant [16,20]. In the aforementioned Dutch study, breast cancer patients experienced a small but significant excess risk of developing a second non-breast cancer including colon cancer [18].
Epidemiological studies have shown a potential association between sex hormones and colorectal cancer. The risk of colorectal cancer in breast cancer patients who may have been exposed to increased levels of endogenous sex hormones and/or exogenous sex hormones (e.g. anti-hormonal therapy) has not been thoroughly evaluated.
Using the National Swedish Cancer Register we established a population-based prospective cohort of breast cancer patients in women diagnosed in Sweden between 1961 and 2010. Subsequent colorectal cancers were identified from the same register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs) were used to estimate the risk of colorectal cancer after a diagnosis of breast cancer. The association between breast cancer therapy and risk of colorectal cancer was evaluated in a subcohort of breast cancer patients treated in Stockholm between 1977 and 2007. Hazard ratios (HRs) and 95%CIs were estimated using Cox regression models.
In a cohort of 179,733 breast cancer patients in Sweden, 2571 incident cases of colorectal cancer (1008 adenocarcinomas in the proximal colon, 590 in the distal colon and 808 in the rectum) were identified during an average follow-up of 9.68 years. An increased risk of colorectal adenocarcinoma was observed in the breast cancer cohort compared with that in the general population (SIR = 1.59, 95%CI: 1.53, 1.65). Adenocarcinoma in the proximal colon showed a non-significantly higher SIR (1.72, 95%CI: 1.61, 1.82) compared with the distal colon (1.46, 95%CI: 1.34, 1.58). In the subcohort of 20,171 breast cancers with available treatment data, 299 cases with colorectal cancers were identified. No treatment-dependent risk of colorectal cancer was observed among the breast cancer patients.
An increased risk of colorectal adenocarcinoma – especially in the proximal colon – was observed in the breast cancer cohort. Breast cancer treatment did not alter this risk.
Issues Related to Colorectal Cancer and Colorectal Cancer Screening Practices in Women
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Whether the occurrence of colon tumors is increased in women with a history of breast cancer is controversial. The SEER registry failed to show an increase in CRC risk in those women with a previous history of breast cancer.37 Similarly, no increase in CRC was found in relatives of Ashkenazi Jews with BRCA1 and BRCA2.38
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In both groups 31.2% of lesions found at colonoscopy in BC patients and 35.3% of the lesions found in the healthy group were right-sided and if we decided to perform a sigmoidoscopy, we could have missed them. Earlier cancer registries [4,5,7,21,22] based studies reported an increased risk for developing CRC among women younger than 45 years at the time of BC diagnosis. In our series, the age at colonoscopy the time since BC diagnosis and colonoscopy and the age at BC diagnosis did not influence the development of adenoma or CRC.
Introduction: The risk of colorectal cancer (CRC) after BC and the additional risk factor of tamoxifen exposure were investigated by several studies with conflicting results. We performed a case-control study aimed at investigating if a past history of breast cancer is a risk factor of developing adenomas or CRC and establishing whether tamoxifen exposure is an additional risk factor. Materials and methods: We enrolled 175 asymptomatic women with a past history of BC and invited them to undergo a screening colonoscopy. In the same period, we enrolled 201 healthy asymptomatic women (HG) with no family history of CRC which were referred to our Unit for a colonoscopy. Results: Mean age at colonoscopy was 56.9 years for BC patients vs. 56.3 years for HG (p = 0.58). In 32/175 (18.3%) BC patients, 38 lesions and in 17/201 (8.4%) controls, 20 lesions (p = 0.029) were diagnosed. BC patients had 5/32 CRC vs. no CRC in the HG. Multivariate analysis of age, family history of CRC, timing from BC diagnosis and first colonoscopy, tamoxifen treatment revealed that none of the variables were predictive of the presence or absence of adenomas or CRC in the BC group. Discussion: In the present study BC group had a significant higher prevalence of adenoma or CRC than controls. Tamoxifen exposure did not increase the risk of adenoma or CRC. Our data support the hypothesis that BC is a risk condition for adenomas or CRC. The risk is small but present and a screening colonoscopy should be offered to these patients.

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ArticlesRisk of colorectal cancer after breast cancer

Summary

Background

Methods

Findings

Interpretations

Introduction

Section snippets

Patients

Results

Discussion

Clin Office Pract

Am J Med

Lancet

J Clin Epidemiol

Cancers of the large intestines

Are women with breast cancer more likely to develop colorectal cancer?

J Clin Gastroenterol

Are women with breast, endometrial, or ovarian cancer at increased risk for colorectal cancer?

Am J Gastroenterol

Appropriateness of colonoscopy: screening for colorectal cancer in asymptomatic individuals

Endoscopy

A simple computer program for generating person-time data in cohort studies involving time-related factors

Am J Epidemiol

Another shortcut method for calculating the confidence interval of a Poisson variable