A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription.

Bulun, Serdar E.; Price, Thomas M.; Aitken, Jane; Mahendroo, Mala; Simpson, Evan R.

doi:10.1210/jcem.77.6.8117355

Cited by 172 publications

(129 citation statements)

References 18 publications

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“…[43][44][45][46] Some studies suggest that locally increased estrogen levels promote tumor growth. [47][48][49] Obesity causes an increased production of the estrogen known as estrone via the aromatization of androstenedione in peripheral adipose tissue. 46,50 In addition, obesity is associated with low levels of sex hormone-binding globulin, which results in a significantly higher level of the biologically active, unbound form of estrogen known as estradiol.…”

Section: Discussionmentioning

confidence: 99%

Body mass and stage of breast cancer at diagnosis

Cui

Whiteman

Flaws

et al. 2001

Intl Journal of Cancer

153

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Obesity is a well-known risk factor for postmenopausal breast cancer. In contrast, the relationship between obesity and stage of breast cancer at diagnosis is less clear. We hypothesized that increased breast size in obese women may delay discovery of breast tumors. Thus, the purpose of our study was to examine whether there is an association between body mass and stage of breast cancer at diagnosis using hospital medical records. Newly diagnosed breast cancer cases (n ‫؍‬ 966) in the Baltimore metropolitan area from 1991 to 1997 were included in our study. Obesity is a well-known risk factor for breast cancer, with the effect being limited to postmenopausal women. [1][2][3][4][5][6][7][8][9] In premenopausal women, there is an inverse association between body mass and the risk of breast cancer, i.e., obese women are less likely to get breast cancer than nonobese women. In contrast, the relationship between obesity and stage at diagnosis in either premenopausal or postmenopausal women is less clear. This is partially because this relationship has not been studied in detail and the results from existing studies are equivocal. For example, several 10 -20 but not all 21,22 studies report that being overweight is associated with late stage at diagnosis. In addition, some studies report that both large tumor size and lymph node involvement are associated with higher body weight, 16,23,24 whereas other studies report that tumor size, but not lymph node involvement are associated with higher body weight. 17,[25][26][27][28] Furthermore, 1 study has reported that lymph node involvement, but not tumor size, is associated with obesity. 29 In obese women with larger breasts, palpation for lumps may be more difficult, resulting in delay in detection and diagnosis of breast cancer. This idea is supported by studies showing that women with large breasts (or bra size as a surrogate) are more likely to be diagnosed at a later stage of breast cancer than women with small breasts. 18,28,30 A study by Reeves et al. 11 reported that the positive association between body mass index (BMI) and stage was confined to tumors that were detected by women themselves. In a recent study, however, Hall et al. 18 reported that the observed positive association was not modified by method of detection.The purpose of our study was to help clarify the relationship between body mass and breast cancer by determining whether there is an association between obesity and stage of breast cancer at diagnosis. We also wished to determine whether there is a positive association between obesity and each of the 3 components for tumor staging (tumor size, node status and distant metastasis) and to explore whether the association between obesity and tumor stage was modified by age. MATERIAL AND METHODS Study subjectsThis is a case series study of breast cancer using data from hospital medical records. Breast cancer cases were obtained from 2 hospitals in the Baltimore metropolitan area. Although all recorded cases of breast cancer were obtained by the investig...

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Section: Discussionmentioning

confidence: 99%

Body mass and stage of breast cancer at diagnosis

Cui

Whiteman

Flaws

et al. 2001

Intl Journal of Cancer

153

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“…28 For example, we and others have shown that preadipocytes are a significant source of local estrogens and likely contribute to obesity-associated breast cancer risk in postmenopausal women. 29–31 Likewise, mature adipocytes promote tumor growth and invasiveness through adipocyte-produced proteins and lipid metabolites. 32–36 In addition to direct tumor-adipose communications, recent studies also suggest cancer-promoting functions of adipocytes through their ability to influence the behaviors of other components in the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer

Sun

Gupta

et al. 2018

OncoImmunology

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Programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) modulate antitumor immunity and are major targets of checkpoint blockade immunotherapy. However, clinical trials of anti-PD-L1 and anti-PD-1 antibodies in breast cancer demonstrate only modest efficacy. Furthermore, specific PD-L1 contributions in various tissue and cell compartments to antitumor immunity remain incompletely elucidated. Here we show that PD-L1 expression is markedly elevated in mature adipocytes versus preadipocytes. Adipocyte PD-L1 prevents anti-PD-L1 antibody from activating important antitumor functions of CD8+ T cells in vitro. Adipocyte PD-L1 ablation obliterates, whereas forced preadipocyte PD-L1 expression confers, these inhibitory effects. Pharmacologic inhibition of adipogenesis selectively reduces PD-L1 expression in mouse adipose tissue and enhances the antitumor efficacy of anti-PD-L1 or anti-PD-1 antibodies in syngeneic mammary tumor models. Our findings provide a previously unappreciated approach to bolster anticancer immunotherapy efficacy and suggest a mechanism for the role of adipose tissue in breast cancer progression.

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“…Many epidemiological and experimental studies showed that estrogens were the fuel behind the aetiology of breast cancer and about 60% of pre-menopausal and 75% of post-menopausal patients with breast cancer had estrogen dependent carcinomas [14]. Estrogen synthesis, metabolism, and signaling are considered to be the basic carcinogenic mechanism of breast cancer [15]. The results of this study showed that changes in the peak aromatase and steroid sulfatase mRNA levels had no correlation with the incidence-age curve in China.…”

Section: Discussionmentioning

confidence: 99%

Aromatase and steroid sulfatase mRNA expression in fine needle aspirates from benign and malignant breast disorders

Gao

Liu

et al. 2012

Chin. Sci. Bull.

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The fine needle aspiration (FNA) test is a convenient and tolerable technique with minimal invasion that is accepted by most women. Local estrogen synthesis depends mainly on the aromatase and steroid sulfatase pathways that are believed to play important roles in breast carcinogenesis. However, little is known about the level of aromatase and steroid sulfatase mRNA expression in FNA samples which contain only small amounts of tissue. The nested Q-PCR assay has been proven to be a highly sensitive and specific method to assess the aromatase expression of breast tissue. In this study, aromatase and steroid sulfatase mRNA expression in 74 patients with benign or malignant disorders was evaluated and compared using nested Q-PCR and non-nested Q-PCR assays. The expression levels were analyzed and correlated with clinical parameters. No difference in the aromatase expression levels between nested and non-nested Q-PCR was noticed. Age and aromatase mRNA expression level were two independent risk factors for breast cancer (P=0.04 and P=0.00, respectively), while menopausal status and steroid sulfatase mRNA expression levels were not associated with breast cancer. This study showed that both nested and non-nested Q-PCR assays were effective methods for research using FNA breast samples.aromatase, steroid sulfatase, breast disorders, fine needle aspirate, nested Q-PCR

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A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription.

Cited by 172 publications

References 18 publications

Body mass and stage of breast cancer at diagnosis

Body mass and stage of breast cancer at diagnosis

Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer

Aromatase and steroid sulfatase mRNA expression in fine needle aspirates from benign and malignant breast disorders

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