Elsevier

Gynecologic Oncology

Volume 130, Issue 2, August 2013, Pages 340-345
Gynecologic Oncology

Risk of second primary cancer among women with breast cancer: A population-based study in Granada (Spain)

https://doi.org/10.1016/j.ygyno.2013.04.057Get rights and content

Highlights

  • We examined risk of second primary cancers in women diagnosed with a first primary breast cancer in Granada (Spain).

  • This is the first Spanish population-based study on this issue, comprising a total of 5897 breast cancer cases.

  • Women diagnosed with breast cancer have higher second cancer incidence, although risk differs by age and second cancer site.

Abstract

Objective

The higher risk of developing new cancers in breast cancer survivors is a public health concern. Our aim was to examine risk of second primary cancers among women diagnosed with breast cancer.

Methods

We studied two cohorts of female cancer patients identified in a population-based cancer registry in Granada (Spain): women first diagnosed with a primary breast cancer (n = 5897) and those with a primary cancer in another site (n = 22,814), followed during 1985–2007 for second cancers and breast cancer occurrence, respectively. We used Standardized Incidence Ratios (SIRs) to estimate second cancer risk by age (< 50 y, ≥ 50 y), time since diagnosis (≤ 5 y, > 5 y) and calendar periods (≤ 1995, > 1996). SIR for breast cancer was calculated in the second cohort.

Results

The risk of developing second cancers (n = 314) was 39% higher (95% CI = 1.23–1.54) among breast cancer patients, and particularly high among women under 50 (SIR = 1.96, 95% CI = 1.48–2.44). Excess risk for endometrial cancer (SIR = 3.04, 95% CI = 2.14–3.94) was statistically significant and remained so in women over 50. Younger women were at higher risk of second ovarian cancer (SIR = 4.90, 95% CI = 1.27–8.53). Increased SIRs were observed during the first five years after breast cancer diagnosis, whereas SIRs decreased thereafter. Breast cancer incidence (n = 171) was not higher among women previously diagnosed with other cancer types (SIR = 0.86, 95% CI = 0.74–1.00).

Conclusion

Women diagnosed with breast cancer have a higher incidence of second primary cancers, particularly of endometrial cancer in women over 50 at diagnosis, and ovarian cancer in younger women. These findings may be explained by treatment-related effects or shared risk factors.

Introduction

Estimates of cancer incidence and mortality in Europe in 2012 show that breast cancer remains the most common cancer and cause of cancer-related death in women, with approximately 464,000 new cases diagnosed in 2012 [1]. In Spain, estimates suggest that 27,000 new breast cancers will be diagnosed by 2012 [2], breast cancer also being the leading cause of death from cancer [1].

According to EUROCARE studies, in Europe, the mean 5-year survival rate of women with breast cancer has increased from 76% in 1990–1994 to 79% in 1995–1999 [3], [4]. Early detection of cancer, better access to care, and availability of adequate treatments may have led to improved survival rates [4].

From the late 1980s until the early 2000s incidence rates have also been rising in Spain, while mortality rates have declined since 1993 [5], [6]. Although the upward trend in incidence has been attributed to lifestyle changes, the decline in mortality [5], [6], [7] may be due to advances in cancer treatment and the consolidation of population-based screening programs. The long-term health of these women has become an important public health issue because the likelihood of developing a second primary cancer may be on the rise. Increased risk for Multiple Primary Tumors (MPT) has been related to various factors, such as a common etiology between cancers (i.e. genetic, environmental or hormonal factors), a consequence of breast cancer treatments, or even chance [8].

Several population-based cancer registry studies [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19] and multicenter cancer registry studies [20], [21] have shown that in comparison to the overall population, women diagnosed with a previous breast cancer have a higher risk of developing a second primary cancer. Elevated risks have been reported for the following cancer sites: endometrium [12], [17], [20], ovary [11], [14], [18], [19], [20], [21], skin melanoma [16], [21], stomach [11], [20], [21], colon and rectum [11], [20], [21], thyroid gland [14], [16], [18], [20], [21], lung [11], [16], [20], [21], soft tissue sarcomas [11], [21], [21], and leukemias [11], [15], [16], [20], [21], among others.

Since incidence and mortality trends vary by age, age-differences in risk for second cancers are also plausible. Some studies have examined risk estimates by age groups [10], [14], [15], [16], [20], [21]. Overall, women diagnosed with breast cancer at premenopausal age were at higher risk of developing a second primary non-breast cancer, with an excess increased risk ranging from 18% to as high as three- or four-fold. Distribution of cancer sites also appears to vary by age, but there is no consistency across studies. Risk estimations based on time since first breast cancer diagnosis have also yielded inconsistent results. In some studies risk increased during a short period after breast cancer diagnosis (1 to 5 years) [9], [14] while opposite findings were reported in others [12], [20].

In Spain, risk of second primary cancers following a first primary breast cancer has not yet been evaluated at the population level. This study aims to assess the risk of second primary cancers in women diagnosed with a first primary breast cancer in Granada Province between 1985 and 2007, and examines the influence of age at diagnosis, time since diagnosis of the first primary cancer, and calendar periods. Additionally, to explore whether second primary cancers were caused by shared risk factors or by treatment side effects, the risk of breast cancer occurrence after a first primary non-breast cancer was also examined.

Section snippets

Population

The study population was derived from a population-based cancer registry located in southern Spain, the Granada Cancer Registry, covering 880,000 inhabitants (447,000 women) [22].

6020 women residing in Granada Province were diagnosed with an invasive first primary breast cancer between 1 January 1985 and 31 December 2007. Breast cancers were defined according to the International Classification of Diseases for Oncology, 3rd Edition, ICD-O-3 (code: C50). We excluded patients whose first primary

Second primary cancer after first primary breast cancer

5897 women were diagnosed with a first primary breast cancer in Granada Province during 1985–2007 and 314 of them subsequently developed a second primary cancer. Table 1 shows the distribution of these cases by age at diagnosis of the first primary breast cancer, calendar year, summation of person-years of follow-up and mean follow-up time. Of the 4170 women diagnosed with primary breast cancer at postmenopausal age (≥ 50 years), 251 were diagnosed with a second primary cancer. Mean age at first

Discussion

This is the first Spanish population-based study of second cancer risk among female breast cancer survivors. Using data from the Granada Cancer Registry (Southern Spain), it is based on nearly 6000 breast cancer cases followed for second primary cancers within the period 1985–2007. Women diagnosed with a first primary breast cancer in Granada had a 39% excess risk of developing a second primary cancer, in comparison with the general population of Spanish women. By age group, risk was notably

Conflict of interest statement

The authors declare that they have no conflict of interest. Disclosures: none.

Role of the funding source

This study has been supported by the Spanish Regional Government of Andalucia: Consejería de Economía, Innovación y Ciencia (CTS-3935, CTS-177) and Consejería de Salud y Bienestar Social de la Junta de Andalucía (Grant DP-0024-2011).

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