Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk

Angeli, Alberto; Dogliotti, Luigi; Naldoni, Carlo; Orlandi, Fabio; Puligheddu, B.; Caraci, P.; Bucchi, Lauro; Torta, M.; Bruzzi, Paolo

doi:10.1016/0960-0760(94)90276-3

Cited by 30 publications

(32 citation statements)

References 29 publications

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“…In addition, clinical follow-up studies have indicated that the presence of cysts increases the risk for subsequent development of breast cancer (8, 44 -47). In particular, women with type I apocrine cysts have been reported to have a 2-4 times higher risk for breast cancer development as compared with women with type II cysts (23,48). The latter observations have been contested by Dixon et al (47), who reported that all women with breast cysts are at increased risk of breast cancer irrespective of the cyst type.…”

Section: And References Therein)mentioning

confidence: 57%

Apocrine Cysts of the Breast

Celis

Gromov

Moreira

et al. 2006

Molecular & Cellular Proteomics

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Up to one-third of women aged 30 -50 years have cysts in their breasts and are presumed to be at increased risk of developing breast cancer. Here we present an extensive proteomic and immunohistochemistry (IHC) study of breast apocrine cystic lesions aimed at generating specific biomarkers and elucidating the relationship, if existent, of apocrine cysts with cancer phenotype. To this end we compared the expression profiles of apocrine macrocysts obtained from mastectomies from high risk cancer patients with those of cancerous and non-malignant mammary tissue biopsies collected from the same patients. We identified two biomarkers, 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase, that were expressed specifically by apocrine type I cysts as well as by apocrine metaplastic cells in type II microcysts, terminal ducts, and intraductal papillary lesions. No expression of these markers was observed in non-malignant terminal ductal lobular units, type II flat cysts, stroma cells, or fat tissue as judged by IHC analysis of matched non-malignant tissue samples collected from 93 high risk patients enrolled in our cancer program. IHC analysis of the corresponding 93 primary tumors indicated that most apocrine changes have little intrinsic malignant potential, although some may progress to invasive apocrine cancer. None of the apocrine lesions examined, however, seemed to be a precursor of invasive ductal carcinomas, which accounted for 81% of the tumors analyzed. Our studies also provided some insight into the origin, development, and enlargement of apocrine cysts in mammary tissue. The successful identification of differentially expressed proteins that characterize specific steps in the progression from early benign lesions to apocrine cancer opens a window of opportunity for designing and testing new approaches for pharmacological intervention, not only in a therapeutic setting but also for chemoprevention, to inhibit cyst development as both 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase are currently being targeted for chemoprevention strategies in various malignancies. Molecular & Cellular Proteomics 5:462-483, 2006.The human breast presents many benign lesions that involve both the glandular and stromal tissues. These include fibrocystic changes, benign breast tumors, and breast inflammatory disease (1). Fibrocystic changes affect more than 50% of women during their lifetime and are comprised of cystic dilation of ducts, apocrine metaplasia of ductal epithelium, fibrosis, adenosis, and intraductal epithelial proliferation (Ref. and references therein).Cysts are fluid-filled sacs that usually develop in the upper half of the breast and are most common in women between 30 and 50 years of age (3). They are also found in menopausal women on hormone replacement therapy. Cysts start as a microscopic dilation of the ductules (microcyst) but can enlarge and reach sizes of a couple of centimeters in diameter (macrocysts) causing pain and discomfort due to the tens...

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Section: And References Therein)mentioning

confidence: 57%

Apocrine Cysts of the Breast

Celis

Gromov

Moreira

et al. 2006

Molecular & Cellular Proteomics

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“…Origin of apocrine tumours: relationship between benign apocrine metaplasia and apocrine carcinomas Apocrine differentiation of breast epithelial cells has attracted a great deal of attention as up to 50% of breast invasive carcinomas exhibit areas with apocrine morphology features [22][23][24][25][26][27][28], and because available data have shown that women with breast apocrine cystic disease have an increased propensity for developing breast cancer later in their lives [29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Molecular pathology of breast apocrine carcinomas: A protein expression signature specific for benign apocrine metaplasia

et al. 2006

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Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0.5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein expression signature distinctive for benign apocrine metaplasias and apocrine cystic lesions. These studies have also presented compelling evidence for a direct link, through the expression of the prostaglandin degrading enzyme 15-PGDH, between early apocrine lesions and pure apocrine carcinomas. Moreover, specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG-CoA reductase, and cyclooxygenase 2 (COX-2) has opened a window of opportunity for pharmacological intervention, not only in a therapeutic manner but also in a chemopreventive setting. Here we review published and recent results in the context of the current state of research on breast apocrine cancer.

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“…Hormonal content or the steroid biochemistry of BCF has also been found to be different in the two types. Increased levels of androsterone-3-α, 17-β-diol glucuronide, dihydroepiandrosterone sulphate (DHEA), oestrogen sulphate, androsterone glucuronide, testosterone and dihydrotestosterone are found in type 1 cysts as compared to type 2 cysts [6].…”

Section: Discussionmentioning

confidence: 98%

“…Type 2 breast cyst fluids have increased levels of progesterone and pregnenolone [6]. The influence of hormonal status of the patients with cystic diseases has also an impact on cyst fluid and breast cancer risk [7].…”

Section: Discussionmentioning

confidence: 99%

Determinants of Malignant Transformation in Fibrocystic Disease of Breast

Vagholkar¹

2014

ABCR

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Background: Fibrocystic disease of the breast in one of the commonest diseases in women above 30 years of age. The assumption of it being innocuous and benign is questionable with increased incidence of malignancies developing in these women. Introduction: Understanding the pathophysiology of fibrocystic disease is essential for identifying determinants of malignant change. Case Report: A case of carcinoma of breast developing in a longstanding and recurrent fibrocystic disease is reported. Discussion: The pathological changes including the influence of hormones on the natural history of the disease are discussed to identify the determinants of malignant transformation. Conclusion: Breast cyst fluid, patterns of cellular lining of the cysts, multiplicity, recurrence and patterns of cellular morphology are important determinants of malignant change.

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Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk

Cited by 30 publications

References 29 publications

Apocrine Cysts of the Breast

Apocrine Cysts of the Breast

Molecular pathology of breast apocrine carcinomas: A protein expression signature specific for benign apocrine metaplasia

Determinants of Malignant Transformation in Fibrocystic Disease of Breast

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