Reproductive history and risk of second primary breast cancer: The WECARE study

Memorial Sloan-Kettering Cancer Center, New York, New York, United States
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 06/2007; 16(5):906-11. DOI: 10.1158/1055-9965.EPI-06-1003
Source: PubMed

ABSTRACT Women with an initial breast cancer diagnosis are at elevated risk of developing subsequent cancer in the contralateral breast. Studies of reproductive factors and contralateral breast cancer (CBC) have provided inconsistent results.
We employed a case-control study nested within five population-based cancer registries in the United States and Denmark to examine associations between reproductive history and CBC risk. Cases were women with asynchronous CBC who had their first primary invasive breast cancer before age 55 years. Two controls, who had only one primary breast cancer diagnosis, were individually matched to each case on age and year of diagnosis, race, and registry. A total of 694 case-control triplets and 11 case-control pairs were enrolled. Information regarding possible CBC risk factors was obtained via telephone interviews. Multivariable conditional logistic regression was used to estimate rate ratios (RR) and 95% confidence intervals (95% CI) associated with risk factors of interest.
Increasing number of full-term pregnancies (FTP) was inversely associated with CBC risk (P trend, 0.001). Women who reported menarche before age 13 years had an increased risk of CBC (RR, 1.26; 95% CI, 1.01-1.58). Age at first FTP, breastfeeding history, and age at menopause were not significantly associated with CBC risk.
These results suggest age at menarche and parity, which are established risk factors for first primary breast cancer, are associated with CBC, whereas other reproductive risk factors associated with first primary breast cancer, such as age at first FTP, are less important factors in the development of CBC.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The extent of the problem The number of cancer survivors has been increasing dramatically and is expected to keep growing in the near future. In the Netherlands, a 38% increase of cancer survivors is estimated from 2005 to 2015, representing an increase from 500,000 to 692,000 (ex-) patients in this period.1 It is well known that individuals who suffered from cancer exhibit a 20% higher risk of subsequent primary malignancies.2 Thus, as the number of cancer survivors increases, the number of patients with multiple primary cancers will increase as well. Because cancer is more frequent among the elderly, the ageing of the Dutch population will cause a further increase in the number of cases with multiple cancers: Only 5%-12% of cancer patients aged 50-64 were previously diagnosed with cancer, versus 12%-26% of those aged over 803. Other forces, including increased awareness of (second) malignancies, the higher use and sensitivity of diagnostic/detection methods, and the recent improvements in cancer treatment and survival will further lead to higher prevalence of multiple cancers. Cancer survivors who develop a second malignancy have a higher risk of dying4 and experience a worsening in their quality of life. Thus, increased interest in second cancer from the epidemiological and clinical perspective is highly relevant.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Overall survival of early-stage breast cancer (BC) patients is similar for those who undergo breast conserving therapy (BCT) and mastectomy, however, 10-15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with BC subtype. Understanding the gene expression of the cancer-adjacent tissue and the stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk. Methods: We utilized two independent data sets to study gene expression data in cancer-adjacent tissue from invasive BC patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific BC subtypes. Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically-normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple negative (Claudin-low or Basal-like) tumors exhibit increased expression of genes involved in inflammation and immune response. While such changes could reflect distinct immune populations present in the microenvironment, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, while triple negative BCs are associated with upregulated immune response genes, Luminal breast cancers are more commonly associated with estrogen-response pathways in adjacent tissues. Conclusions: Specific characteristics of BCs are reflected in the surrounding histologically-normal tissue. This commonality between tumor and cancer-adjacent tissue may underlie second primaries and local recurrences. Impact: Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. Copyright © 2014, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 12/2014; 24(2). DOI:10.1158/1055-9965.EPI-14-0934 · 4.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An increasingly large proportion of women with unilateral breast cancer are treated with bilateral mastectomy. The rationale behind bilateral surgery is to prevent a second primary breast cancer and thereby to avoid the resultant therapy and eliminate the risk of death from contralateral breast cancer. Bilateral mastectomy has been proposed to benefit women at high risk of contralateral cancer, such as carriers of BRCA1 and BRCA2 mutations, but for women without such mutations, the decision to remove the contralateral breast is controversial. It is important to evaluate the risk of contralateral breast cancer on an individual basis, and to tailor surgical treatment accordingly. On average, the annual risk of contralateral breast cancer is approximately 0.5%, but increases to 3% in carriers of a BRCA1 or BRCA2 mutation. Risk factors for contralateral breast cancer include a young age at first diagnosis of breast cancer and a family history of breast cancer. Contralateral mastectomy has not been proven to reduce mortality from breast cancer, but the benefit of such surgery is not expected to become apparent until the second decade after treatment. An alternative to contralateral mastectomy is adjuvant hormonal therapy (such as tamoxifen), but the extent of risk reduction is smaller (approximately 50%) compared to 95% or more for contralateral mastectomy. This Review focuses on the risk factors for contralateral breast cancer, and discusses the evidence that bilateral mastectomy might reduce mortality in patients with unilateral breast cancer.
    Nature Reviews Clinical Oncology 02/2014; DOI:10.1038/nrclinonc.2014.3 · 15.70 Impact Factor

Full-text (2 Sources)

Available from
May 17, 2014