Late age at first full term birth is strongly associated with lobular breast cancer

University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin, USA.
Cancer (Impact Factor: 4.89). 05/2011; 117(9):1946-56. DOI: 10.1002/cncr.25728
Source: PubMed

ABSTRACT Late age at first full-term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades.
The purpose of this population-based case-control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal-lobular breast cancer diagnosis in association with AFB and nulliparity.
AFB ≥30 years was associated with a 2.4-fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9-2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2-1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3-2.2) than for ductal (OR, 1.2; 95% CI, 1.1-1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer.
Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer.

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    • "Nulliparity may be associated with ovulatory disorders in the majority of cases and there are studies, which equivocally exhibited increased prevalence of breast cancer in nulliparous women [161, 162]. Furthermore, coexistence of nulliparity and overweight may amplify each other’s effect on increasing breast cancer risk having strong synergism [161]. "
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    ABSTRACT: Literary data suggest apparently ambiguous interaction between menopausal status and obesity-associated breast cancer risk based on the principle of the carcinogenic capacity of estrogen. Before menopause, breast cancer incidence is relatively low and adiposity is erroneously regarded as a protective factor against this tumor conferred by the obesity associated defective estrogen-synthesis. By contrast, in postmenopausal cases, obesity presents a strong risk factor for breast cancer being mistakenly attributed to the presumed excessive estrogen-production of their adipose-tissue mass. Obesity is associated with dysmetabolism and endangers the healthy equilibrium of sexual hormone-production and regular menstrual cycles in women, which are the prerequisites not only for reproductive capacity but also for somatic health. At the same time, literary data support that anovulatory infertility is a very strong risk for breast cancer in young women either with or without obesity. In the majority of premenopausal women, obesity associated insulin resistance is moderate and may be counteracted by their preserved circulatory estrogen level. Consequently, it is not obesity but rather the still sufficient estrogen-level, which may be protective against breast cancer in young adult females. In obese older women, never using hormone replacement therapy (HRT) the breast cancer risk is high, which is associated with their continuous estrogen loss and increasing insulin-resistance. By contrast, obese postmenopausal women using HRT, have a decreased risk for breast cancer as the protective effect of estrogen-substitution may counteract to their obesity associated systemic alterations. The revealed inverse correlation between circulatory estrogen-level and breast cancer risk in obese women should advance our understanding of breast cancer etiology and promotes primary prevention measures. New patents recommend various methods for the prevention and treatment of obesity-related systemic disorders and the associated breast cancer.
    10/2012; 8(2). DOI:10.2174/157489213805290628
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    • "A meta-analysis of 9 cohort or case–control studies also revealed a reduced risk among patients with hormone receptor-positive cancers [17]. This protective effect was also observed in lobular carcinomas that are often positive for hormone receptors [25]. In this context, the relative protective effect of young age of first full-term birth has been observed mainly for postmenopausal women [17, 23, 24, 26]. "
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    ABSTRACT: The fact that reproductive factors have significant influence on the risk of breast cancer is well known. Early age of first full-term birth is highly protective against late-onset breast cancers, but each pregnancy, including the first one, increases the risk of early-onset breast cancer. Estradiol and progesterone induce receptor activator of NF-kappa B ligand (RANKL) in estrogen receptor (ER)- and progesterone receptor (PgR)-positive luminal cells. RANKL then acts in a paracrine fashion on the membranous RANK of ER/PgR-negative epithelial stem cells of the breast. This reaction cascade is triggered by chorionic gonadotropin during the first trimester of pregnancy and results in the morphological and functional development of breast tissue. On the other hand, the administration of non-steroidal anti-inflammatory drugs in the early steps of weaning protects against tumor growth through reduction of the acute inflammatory reaction of post lactation remodeling of breast tissue. This is experimental evidence that may explain the short-term tumor-promoting effect of pregnancy. The protective effect of prolonged breast feeding may also be explained, at least in a part, by a reduced inflammatory reaction due to gradual weaning. Delay of first birth together with low parity and short duration of breast feeding are increasing social trends in developed countries. Therefore, breast cancer risk as a result of reproductive factors will not decrease in these countries in the foreseeable future. In this review, the significance of reproductive history with regard to the risk of breast cancers will be discussed, focusing on the age of first full-term birth and post lactation involution of the breast.
    Breast Cancer 06/2012; 19(4):302-8. DOI:10.1007/s12282-012-0384-8 · 1.59 Impact Factor
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    ABSTRACT: To evaluate the prognostic value of preoperative serum tetranectin (TN) in Danish ovarian cancer (OvCa) patients. Design. Population-based, multidisciplinary Danish case-control study of OvCa. A total of 445 primary OvCa patients diagnosed at one of the gynecological departments in 18 regional hospitals around Denmark during the period 1994-1999. Serum levels of TN were evaluated preoperatively and tested for possible association with prognosis. Disease specific survival. During the observation period (median 45.9 months, range 0.2-121) 278 OvCa-related deaths were seen. Univariate analysis of TN and CA125 demonstrated a significant association with survival using the Cox proportional hazards model, when stratified for adjuvant treatment (TN: p < 0.0001, hazard ratio = 0.44; 95% confidence interval 0.33-0.60 and CA125: p < 0.0001, hazard ratio = 1.19; 95% confidence interval 1.11-1.27). Disease specific survival curves for patients with tumors in the early stages showed no significant association with survival, neither for TN (p = 0.68) nor for CA125 (p = 0.07). For the stage III group, a significant association with survival was found for TN (p = 0.027), but not for CA125 (p = 0.37). Multivariate Cox analysis identified TN, age, residual tumor, International Federation of Gynecology and Obstetrics stage and grade but not serum CA125 as independent prognostic variables. Preoperative serum TN is a useful prognostic indicator of advanced stage for patients with OvCa.
    Acta Obstetricia Et Gynecologica Scandinavica 02/2010; 89(2):190-8. DOI:10.3109/00016340903530936 · 2.43 Impact Factor
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