Personal history of breast cancer as a significant risk factor for endometrial serous carcinoma in women aged 55 years old or younger

Abstract

A comparative study between endometrial serous carcinoma (ESC) and endometrial endometrioid carcinoma (EEC) was performed to determine whether a personal history of breast cancer is a risk factor for ESC in women aged 55 yr. Study subjects consisted of 348 women who were diagnosed with ESC and 830 comparison subjects who had EEC. Variables studied included age at diagnosis, a history of breast cancer, tamoxifen therapy, hormonal replacement therapy and smoking history. Overall, 19.4% of women with ESC had a history of breast cancer, which was significantly higher than that of 3% in comparison subjects. Among the study subjects, the incidence of a prior breast cancer was significantly higher in patients who were 55 yr of age or younger (41.5%) than those who were older than 55 yr (16%). The statistical significance of both of the aforementioned comparisons was independent of tamoxifen usage on multivariate analyses. The mean time interval between prior breast cancer and endometrial cancer was 92.5 mo (range 7-240 mo) in the study group and 79 mo (range 7-192 mo) in the comparison group. For the whole cohort and individual subgroups (ESC, EEC, 55 yr and >55 yr), a personal history of breast cancer did not adversely affect the patient outcomes, which was largely dependent on standard clinicopathologic parameters such as International Federation of Gynecology and Obstetrics stage, as has previously been demonstrated. These findings suggest that a personal history of breast cancer may be a significant risk factor for the development of ESC in women aged 55 yr. Further studies are needed to clarify the relationship between these two cancers in this age group and whether this increased risk is reflective of a genetic predisposition.Endometrial carcinoma is the most common malignancy of the female genital tract in the United States.1 This neoplasm represents a relatively heterogeneous group of diseases regarding epidemiology, molecular abnormalities and biologic behavior 2 but can in general be classified into two subtypes, Type I or Type II.3 Endometrial endometrioid adenocarcinoma (EEC) is the prototype of the Type I carcinoma, is the most common histologic subtype of all endometrial malignancies and, overall, has a fairly good prognosis. The development of EEC has been attributed to hyperestrogenism related to a myriad of conditions that range from endogenous (anovulatory cycles, obesity, diabetes and hormone-producing neoplasm) to exogenous [unopposed hormonal replacement therapy (HRT) and use of fertility drugs] to physiologic (late menopause). 4 Unlike EEC, endometrial serous carcinoma (ESC) or uterine papillary serous carcinoma, 5 a prototype of the Type II carcinoma, is less commonly seen but bears a significantly worse prognosis.6-9 Despite numerous research efforts in the past two decades, no clear risk factors have yet been identified for ESC or other variants of Type II endometrial cancers, including clear cell carcinoma (CCC).

Etiologic heterogeneity in endometrial cancer: Evidence from a Gyneco- logic Oncology Group trial

“…A number of previous studies have noted the development of uterine serous cancers among women with breast cancer [7,[36][37][38][39], but our results expand on these findings by showing that breast cancer predisposes to serous cancers as well as carcinosarcomas and grade 3 endometrioid tumors. Several hypotheses have been proposed for the excess of endometrial cancers among women with prior breast cancer, including similar risk profiles, radiation treatment of proximate organs, manifestations of rare inherited cancer syndromes (e.g., Li-Fraumeni and Lynch syndromes), or the result of mutations in cancer predisposing genes [40,41].…”

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

“…Our study comprises a lower mean value of age, which is revealed that the disease occurs a decade earlier, as compared to western countries (Sandhu et al, 2010). The probable reason for the early onset of this dreaded disease in the younger women may be due to personal history with a breast cancer/ovary cancer (Liang et al, 2011), family history of breast cancer, particularly in a mother, sister and daughter (Metcalfe et al, 2010), history of radiation therapy to the chest before age 40. (Narod, 2011) The aim of the mutational research analysis was to study the incidences and distribution of mutations in North-Eastern region of India concerning the other factors relating for breast cancer.…”

Endometrial Intraepithelial Neoplasia

“…Definitive risk factors for type II endometrial cancer are still unclear, however. In one recent study, we found that women 55 years of age or under with a personal history of breast cancer, had an increased risk of ESC as compared with controls (Liang, Pearl et al 2010), and an earlier study by Chan et al came to comparable conclusions 2006 (Chan, Manuel et al 2006). These Type II cancers, most notably ESC, also exhibit frequent mutation and overexpression of the p53 (Sherman, Bur et al 1995;Nordstrom, Strang et al 1996) and HER2/neu (Rolitsky, Theil et al 1999) genes and proteins, respectively.…”

“…In 2007, a Swedish study found that 7.28% of patients undergoing genetic counseling for an increased risk of breast cancer, had family histories of both endometrial and breast cancers (von Wachenfeldt, Lindblom et al 2007). We recently published a large cohort study that had found a history of a prior breast cancer in 20% of women with ESC, with the incidence being significantly higher in patients who were 55 years old or younger (41.5%) in comparison to those older than 55 years (16%) (Liang, Pearl et al 2010). …”

“…The approach at our institute is based on our consideration of these patients to be at a significantly higher risk for the development of endometrial malignancy than their counterparts without EmGD, and that this risk is accentuated by factors such as a personal history of breast cancer or BRCA mutations (Chan, Manuel et al 2006;Liang, Pearl et al 2010). For patients without breast cancer history and/or BRCA mutations, if the diagnosis of EmGD is confirmed in a biopsy, we recommend complete dilation and curettage (D&C) for larger sampling.…”