Elsevier

Gynecologic Oncology

Volume 136, Issue 1, January 2015, Pages 158-171
Gynecologic Oncology

Review
Risk of second cancers cancer after a first primary breast cancer: A systematic review and meta-analysis

https://doi.org/10.1016/j.ygyno.2014.10.029Get rights and content

Highlights

  • The scientific evidence and the risk of second primary cancers in women diagnosed with a first breast cancer was examined.

  • This is the first review and meta-analysis in regards to risk of second cancer after breast cancer.

  • Women diagnosed with breast cancer have a 17% higher second cancer risk, with this risk being higher in premenopausal women.

Abstract

Objective

To examine the scientific evidence and the risk of second primary cancers in women diagnosed with a first primary breast cancer.

Methods

The literature was searched in Pubmed and Embase and included studies published up to June 2013, using population-based data and IARC/AICR codification rules for multiple primary cancers. A qualitative synthesis was carried out and the methodological quality of the studies evaluated. Standardised incidence ratios (SIRs) on second cancer risk, weighted by the standard error of each study, were pooled using fixed and random effects models. SIRs were also pooled by age at diagnosis (< 50 and ≥ 50 years), and time since diagnosis of the first breast cancer (< 10 and ≥ 10 years).

Results

15 out of 710 articles fulfilled the inclusion criteria. All of them were retrospective cohort studies either population-based (13 studies) or hospital-based studies (2 studies). The studies varied with respect to number of cases, selection criteria, definition of multiple primary cancers, and the second cancer sites included. SIRs reported in these studies for all cancers combined varied from 1.0 to 1.4. The pooled SIR estimate for second cancer risk was 1.17 (95% CI: 1.10–1.25). By age groups, SIR estimates were 1.51 (95% CI: 1.35–1.70) for women younger than 50 years and 1.11 (95% CI: 1.02–1.21) for those who were older. Women with breast cancer are at risk of second cancers within the first 10 years after the first breast cancer diagnosis (SIR: 1.19; 95% CI: 1.06–1.33), and thereafter (SIR: 1.26; 95% CI: 1.05–1.52).

Conclusion

This higher risk of second cancers in women diagnosed with a first primary breast cancer with respect to the general population emphasises the importance of prevention and control policies aimed at reducing incidence of second cancers.

Introduction

Breast cancer represents a major public health issue worldwide. It is the most commonly diagnosed cancer among women, with 1.38 million new cases estimated in 2012 [1]. In Europe, estimates of cancer incidence and mortality in 2012 show that it remains being the most common cancer and cause of cancer-related death in women [2]. Early detection through systematic screening, better access to care, and advances in treatments have been leading to a decline in mortality rates [3], [4]. Thus, as the number of women who overcome a breast cancer is considerably increasing, the likelihood of developing subsequent cancers, i.e. Multiple Primary Tumours (MPT), becomes higher. Subsequent cancers after an initial breast cancer could be attributed either to common risk factors predisposing to both the first and second cancer, such as genetic predisposition or other identified risk factors, or to treatment-related side effects [5].

Several population-based cancer registry studies [6], [7], [8], [9], [10], [11] as well as studies involving several cancer registries [12], [13], have evaluated the risk of developing second primary cancers among women diagnosed with a first primary breast cancer with respect to the general population. Most of these studies were derived from European data [6], [7], [8], [9], [10], [11], [12], [13] and from the National Cancer Institute's Surveillance, Epidemiology (SEER) cancer registries in the United States [14], [15], [16]. However, risk estimates provided by these studies are largely different, with an overall excess risk ranging between 15 and 45% for all cancer sites combined. Risk differences by age groups have also been examined in some of these studies [7], [10], [11], [12], [13], showing that women diagnosed with breast cancer at premenopausal ages were at higher risk of developing a second cancer. In general, second primary cancers of the endometrium, ovary, melanoma, stomach and colon cancer have been reported to occur more frequently [6], [7], [8], [9], [10], although there is no consensus between studies.

Some studies have also provided risk estimates of second cancers according to treatment of the breast cancer, such as radiotherapy [14], [17], [18], [19], [20], chemotherapy and surgery [17], [18], [19], [20] or hormonal therapy [18], [19], [20], to assess how treatment-related factors may influence this risk. However, as information on treatment is not systematically collected in population-based cancer registries, most of these studies reported risk estimates on a limited number of observed cases with information available on primary treatment for breast cancer. For this reason, calendar year and time since diagnosis of the first breast cancer have been used as a proxy for treatment in some studies [6], [9], [12], [17]. However, results reported by these studies are rather inconsistent as some support an increased risk during the first years after the breast cancer diagnosis [6], [12] whilst others report that risk increases or remains high over time [9], [17].

The aim of the current study is to examine the scientific evidence related to the risk of developing a second primary cancer after a breast cancer diagnosis for all sites combined, by age at breast cancer diagnosis and by time since breast cancer diagnosis, and to further combine the results of these studies by using meta-analysis.

Section snippets

Search strategy

A search was carried out to find relevant studies and reviews published up to 30 June 2013 (no starting date was fixed). The databases used were Pubmed and Embase.

The following MeSH terms related to “second cancers” and “multiple primary cancers” and related subcategories were selected: Neoplasms/Multiple Primary, Neoplasms/Second Primary and epidemiology. A number of key words (“second cancers” and “population-based”) were also used and combined in different databases (Table 1). The reference

Results of the bibliographical search

The defined search criteria in Pubmed and Embase retrieved 710 articles (Fig. 1). 16 articles, identified through manual review of reference lists, were added. 61 articles were ruled out because of duplication, leaving a total number of 665 articles for review. Based on the title and abstract we excluded 583 articles for different causes of exclusions. 82 articles were left for the “in extenso” analysis, of which 67 were further excluded: 11 studies did not use IARC/AICR coding rules for MPC,

Discussion

To the best of our knowledge, this systematic review and meta-analysis, conducted with all the studies available, is the first one to assess the risk of second primary cancers among women previously diagnosed with a first primary breast cancer.

Our results show that these women have a 17% increase in the risk of developing a new primary non-breast cancer in comparison with women without cancer of the general population. This excess in risk is likely to be associated with treatment modalities for

Conclusions

In this review we observed varying results on the magnitude of risk for subsequent cancers after a diagnosis of breast cancer that could be explained by various differences between the published studies, either methodological, such as the definition of second cancers, or inherent to the study populations, such as varying breast cancer treatment protocols between the studies and over time. The qualitative analysis of studies included in this review has revealed that these and other variables may

Conflict of interest

The authors declare that they have no conflict of interest.

Role of the funding source

This study has been supported by the Spanish Regional Government of Andalucia: Consejería Economía, Innovación, Ciencia y Empleo, Junta de Andalucia (CTS-3935, CTS-177).

Author's contributions are as follows

EMM, MR and MJS carried out the review and drafted the manuscript. They also conceived of the study. MJS participated in its coordination. EMM, MFF and ESC conducted the data analysis. MFF, MAM and JE and JPA helped to extract the data and reviewed critically all the studies selected. All authors read and approved the final manuscript.

References (59)

  • K. Hemminki et al.

    Familial risks in second primary breast cancer based on a family cancer database

    Eur J Cancer

    (1999)
  • M. Prochazka et al.

    Lung cancer risks in women with previous breast cancer

    Eur J Cancer

    (2002)
  • R. Langballe et al.

    Risk for second primary non-breast cancer in pre- and postmenopausal women with breast cancer not treated with chemotherapy, radiotherapy or endocrine therapy

    Eur J Cancer

    (2011)
  • J. Ferlay et al.

    GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11, [Internet]

    (2013)
  • K. Hemminki et al.

    Multiple primary cancers as clues to environmental and heritable causes of cancer and mechanisms of carcinogenesis

    IARC Sci Publ

    (2004)
  • H.S. Evans et al.

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

    Br J Cancer

    (2001)
  • I. Soerjomataram et al.

    Primary malignancy after primary female breast cancer in the South of the Netherlands, 19722001

    Breast Cancer Res Treat

    (2005)
  • C. Cluze et al.

    Incidence of second cancer within 5 years of diagnosis of a breast, prostate or colorectal cancer: a population-based study

    Eur J Cancer Prev

    (2009)
  • N. Volk et al.

    Second primary cancers in breast cancer patients in Slovenia

    Cancer Causes Control

    (1997)
  • L. Mellemkjaer et al.

    Risk of second cancer among women with breast cancer

    Int J Cancer

    (2006)
  • L. Mellemkjaer et al.

    Risk of primary non-breast cancer after female breast cancer by age at diagnosis

    Cancer Epidemiol Biomarkers Prev

    (2011)
  • dG Berrington et al.

    Second solid cancers after radiotherapy for breast cancer in SEER cancer registries

    Br J Cancer

    (2010)
  • J.S. Raymond et al.

    Multiple primary tumours in women following breast cancer, 1973–2000

    Br J Cancer

    (2006)
  • G.P. Yu et al.

    Incidences and trends of second cancers in female breast cancer patients: a fixed inception cohort-based analysis (United States)

    Cancer Causes Control

    (2006)
  • C. Rubino et al.

    Increased risk of second cancers following breast cancer: role of the initial treatment

    Breast Cancer Res Treat

    (2000)
  • M. Andersson et al.

    Risk of second primary cancer among patients with early operable breast cancer registered or randomised in Danish Breast Cancer cooperative Group (DBCG) protocols of the 77, 82 and 89 programmes during 1977–2001

    Acta Oncol

    (2008)
  • Y.M. Kirova et al.

    Second malignancies after breast cancer: the impact of different treatment modalities

    Br J Cancer

    (2008)
  • M. Schaapveld et al.

    Risk of new primary nonbreast cancers after breast cancer treatment: a Dutch population-based study

    J Clin Oncol

    (2008)
  • International Agency for Research on Cancer (IARC) et al.

    International Rules for Multiple Primary Cancers (ICD-O-Third Edition)

    (2000)
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