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Breast Cancer Research : BCR Mar 2014A postpartum diagnosis of breast cancer is an independent predictor of metastases, however the reason is unknown. In rodents, the window of postpartum mammary gland...
INTRODUCTION
A postpartum diagnosis of breast cancer is an independent predictor of metastases, however the reason is unknown. In rodents, the window of postpartum mammary gland involution promotes tumor progression, suggesting a role for breast involution in the poor prognosis of human postpartum breast cancers. Rodent mammary gland involution is characterized by the programmed elimination of the secretory lobules laid down in preparation for lactation. This tissue involution process involves massive epithelial cell death, stromal remodeling, and immune cell infiltration with similarities to microenvironments present during wound healing and tumor progression. Here, we characterize breast tissue from premenopausal women with known reproductive histories to determine the extent, duration and cellular mechanisms of postpartum lobular involution in women.
METHODS
Adjacent normal breast tissues from premenopausal women (n = 183) aged 20 to 45 years, grouped by reproductive categories of nulliparous, pregnant and lactating, and by time since last delivery were evaluated histologically and by special stain for lobular area, lobular type composition, apoptosis and immune cell infiltration using computer assisted quantitative methods.
RESULTS
Human nulliparous glands were composed dominantly of small (approximately 10 acini per lobule) and medium (approximately 35 acini per lobule) sized lobules. With pregnancy and lactation, a >10 fold increase in breast epithelial area was observed compared to nulliparous cases, and lactating glands were dominated by mature lobules (>100 acini per lobule) with secretory morphology. Significant losses in mammary epithelial area and mature lobule phenotypes were observed within 12 months postpartum. By 18 months postpartum, lobular area content and lobule composition were indistinguishable from nulliparous cases, data consistent with postpartum involution facilitating regression of the secretory lobules developed in preparation for lactation. Analyses of apoptosis and immune cell infiltrate confirmed that human postpartum breast involution is characterized by wound healing-like tissue remodeling programs that occur within a narrowed time frame.
CONCLUSIONS
Human postpartum breast involution is a dominant tissue-remodeling process that returns the total lobular area of the gland to a level essentially indistinguishable from the nulliparous gland. Further research is warranted to determine whether the normal physiologic process of postpartum involution contributes to the poor prognosis of postpartum breast cancer.
Topics: Adult; Analysis of Variance; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Apoptosis; Breast; Cell Proliferation; Epithelial Cells; Female; Humans; Immune System; Immunohistochemistry; Ki-67 Antigen; Lactation; Leukocyte Common Antigens; Middle Aged; Parity; Postpartum Period; Pregnancy; Premenopause; Young Adult
PubMed: 24678808
DOI: 10.1186/bcr3633 -
Revista Espanola de Patologia :... 2018Adenomyoepitheliomas of the breast are infrequent tumors with a variable histological appearance, and they can mimic several epithelial, myoepithelial and biphasic... (Review)
Review
Adenomyoepitheliomas of the breast are infrequent tumors with a variable histological appearance, and they can mimic several epithelial, myoepithelial and biphasic lesions of the breast. We have reviewed four cases of adenomyoepithelioma of the breast diagnosed between 2005 and 2015 in our institution (Hospital Clínico San Carlos). Mean age was 57years. All lesions were solid irregular masses located in the upper quadrants (3 of them in the right breast and one in the left), with an average size of 13mm. Microscopically 2 of them were tubular and the remaining 2 were lobulated subtypes. Hyaline, myxoid and cystic areas, peripheral pseudoinfiltration and satellite nodules were occasionally seen. Myoepithelial cells were fusiform and immunohistochemically they were actin, calponin, p63, S100 and CD10 positive and CKAE1-AE3 negative, with variable CK23BE12 and CK5/6 staining. In all cases lumpectomy was curative, no recurrences or malignant degeneration were observed.
Topics: Adenomyoepithelioma; Adult; Aged; Breast Neoplasms; Female; Humans; Middle Aged
PubMed: 29290325
DOI: 10.1016/j.patol.2016.12.001 -
The origins of breast cancer associated with mammographic density: a testable biological hypothesis.Breast Cancer Research : BCR Mar 2018Our purpose is to develop a testable biological hypothesis to explain the known increased risk of breast cancer associated with extensive percent mammographic density...
BACKGROUND
Our purpose is to develop a testable biological hypothesis to explain the known increased risk of breast cancer associated with extensive percent mammographic density (PMD), and to reconcile the apparent paradox that although PMD decreases with increasing age, breast cancer incidence increases.
METHODS
We used the Moolgavkar model of carcinogenesis as a framework to examine the known biological properties of the breast tissue components associated with PMD that includes epithelium and stroma, in relation to the development of breast cancer. In this model, normal epithelial cells undergo a mutation to become intermediate cells, which, after further mutation, become malignant cells. A clone of such cells grows to become a tumor. The model also incorporates changes with age in the number of susceptible epithelial cells associated with menarche, parity, and menopause. We used measurements of the radiological properties of breast tissue in 4454 healthy subjects aged from 15 to 80+ years to estimate cumulative exposure to PMD (CBD) in the population, and we examined the association of CBD with the age-incidence curve of breast cancer in the population.
RESULTS
Extensive PMD is associated with a greater number of breast epithelial cells, lobules, and fibroblasts, and greater amounts of collagen and extracellular matrix. The known biological properties of these tissue components may, singly or in combination, promote the acquisition of mutations by breast epithelial cells specified by the Moolgavkar model, and the subsequent growth of a clone of malignant cells to form a tumor. We also show that estimated CBD in the population from ages 15 to 80+ years is closely associated with the age-incidence curve of breast cancer in the population.
CONCLUSIONS
These findings are consistent with the hypothesis that the biological properties of the breast tissue components associated with PMD increase the probability of the transition of normal epithelium to malignant cells, and that the accumulation of mutations with CBD may influence the age-incidence curve of breast cancer. This hypothesis gives rise to several testable predictions.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Breast; Breast Density; Breast Neoplasms; Epithelial Cells; Female; Fibroblasts; Humans; Mammography; Menopause; Middle Aged; Mutation; Risk Factors; Young Adult
PubMed: 29514672
DOI: 10.1186/s13058-018-0941-y -
Journal of Plastic, Reconstructive &... May 2022The inframammary fold defines the shape and structure of the breast, especially in women. As the inframammary fold is placed between the fifth and sixth ribs, the...
The inframammary fold defines the shape and structure of the breast, especially in women. As the inframammary fold is placed between the fifth and sixth ribs, the ligaments or fascia are thought to attach from these ribs. However, the previous literature on what structures constitute the inframammary fold does not provide sufficient knowledge for reconstructing the natural form of the fold. This study aimed to clarify the structure that involves the inframammary fold. Ten sides of five formalin-fixed, adult Asian cadaveric breasts were studied. Upon dissection of the breast, including the ribs, the fat lobules were removed while preserving the septal structures under the microscope. The fascial structures were observed grossly and radiographically. A multilayered fascial structure was noted from the dermis near the inframammary fold, anchored to the deep fascia of the pectoralis major muscle mainly at the height of the fourth rib and partially of the fifth rib, from the outside of the nipple to the linea axillaris media, where the fold could be clearly observed. Additionally, the fat lobules around the inframammary fold were subdivided by thin septa closer to the dermis, and they fused posteriorly and upward to form this fascial structure. The inframammary fold was not formed by an adhesion directly under the sixth rib, but by the skin "hanging" from the height of the fourth and fifth ribs due to the multilayered fascial structure that repeatedly fused and dissociated and the changes in the size of the fat lobules. This new anatomical finding may help in inframammary fold reconstruction.
Topics: Adult; Breast; Fascia; Female; Humans; Ligaments; Mammaplasty; Nipples; Pectoralis Muscles
PubMed: 34998682
DOI: 10.1016/j.bjps.2021.11.109 -
Histopathology Dec 2017Gender dysphoria is a diagnosis whereby an individual identifies as the opposite gender. The management of patients seeking female-to-male (FTM) transition includes...
AIMS
Gender dysphoria is a diagnosis whereby an individual identifies as the opposite gender. The management of patients seeking female-to-male (FTM) transition includes hormonal therapy and surgical intervention, including mastectomy. The aim of this study was to characterize the immunohistological findings in resection specimens from FTM patients.
METHODS AND RESULTS
We reviewed 68 cases (67 patients, one with re-excision) of FTM breast tissue resection by collecting clinical data, reviewing breast imaging and pathology reports (gross fibrous density, specimen weight, and number of cassettes submitted), and reviewing pathology slides [number of tissue pieces submitted, number of terminal duct lobule units (TDLUs), and the presence of histological findings]. Significant histological findings were present in 51 of 68 (75.0%) cases, including one case (1.5%) of flat epithelial atypia. Fibrocystic changes were the most common finding (27/68, 39.7%), followed by gynaecomastoid change, fibrotic stage, (22/68, 32.4%), and fibroadenomatoid change (11/68, 16.2%). Fibrocystic change was associated with increased numbers of TDLUs, and gynaecomastoid change was associated with lower body mass index and decreased numbers of TDLUs. Gynaecomastoid change showed a moderate proportion of luminal epithelial cells with strong-intensity immunohistochemical staining for oestrogen receptor, progesterone receptor, and androgen receptor, and a three-layered epithelium demonstrated by the use of cytokeratin 5/6 immunohistochemistry.
CONCLUSIONS
We identified gynaecomastoid change at a significantly higher rate than previously reported in female patients. We support the continued gross and histological evaluation of FTM specimens in light of the identification of atypia in one case.
Topics: Adult; Breast; Epithelial Cells; Female; Fibrocystic Breast Disease; Gender Dysphoria; Humans; Hyperplasia; Male; Mastectomy; Middle Aged; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Sex Reassignment Surgery; Transgender Persons; Young Adult
PubMed: 28657118
DOI: 10.1111/his.13299 -
Cancer Epidemiology, Biomarkers &... Jun 1994Breast cancer is one of the most frequent malignancies in women, and its incidence is increasing. No reduction in the mortality rate has resulted from advances in early... (Review)
Review
Breast cancer is one of the most frequent malignancies in women, and its incidence is increasing. No reduction in the mortality rate has resulted from advances in early diagnosis and new therapeutic modalities; therefore, new approaches to the understanding of this disease are required. The observation that, in an experimental animal model, full-term pregnancy prior to exposure to a carcinogenic agent protects the mammary gland from malignant transformation led us to study the mechanisms underlying this phenomenon. The protective effect observed after pregnancy did not depend upon gestational or lactational hyperplasia of the mammary gland, but upon structural changes induced in the mammary parenchyma by those processes. Those changes are permanent, since the protective effect is maintained after pregnancy and consists in the complete differentiation of terminal end buds to lobules. The protective effect exerted by pregnancy can be mimicked by treating young virgin rats with a single placental hormone, chorionic gonadotropin. Since the possibility of preventing breast cancer by treating young nulliparous females with hormones that mimic a fullterm pregnancy that results in complete differentiation of the gland is of practical interest to the human female population, we undertook the study of the human breast. The breast of postpubertal nulliparous women is composed of lobular structures reflecting different stages of development. Lobules type 1 (lob 1) are the most undifferentiated ones. Lobules type 2 evolve from the previous ones and have a more complex morphology, being composed of a higher number of ductular structures per lobule. They progress to lobules type 3 and 4, which are present in the pregnant and lactational periods of the mammary gland. In nulliparous women the structure most frequently found at all ages is the lob 1, whereas in parous women, lob 3 is the most frequent one. Lob 1 are considered to be the site of origin of ductal carcinoma in situ, which progresses to invasive carcinoma. Lob 2 originate lobular carcinoma and lob 3 originate adenomas, fibroadenomas, sclerosing adenosis, and apocrine cysts. These observations led us to test if the degree of lobular development influences the transformation of human breast epithelial cells exposed in vitro to chemical carcinogens. We found that primary cultures derived from breast tissues composed of lobules type 1 and 2 express phenotypes of cell transformation which were not observed in cells derived from lobules type 3.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Aging; Animals; Anticarcinogenic Agents; Breast; Breast Neoplasms; Cell Transformation, Neoplastic; Chorionic Gonadotropin; Female; Humans; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Neoplasms, Hormone-Dependent; Parity; Pregnancy; Rats; Risk Factors
PubMed: 8061586
DOI: No ID Found -
Cancer Prevention Research... Nov 2015Estrogen receptor (ER) β is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer...
Estrogen receptor (ER) β is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967-1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P < 0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ERβ expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low-moderate ERβ expression (P = 0.0008). High ERβ expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ERβ may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction.
Topics: Adult; Aged; Aged, 80 and over; Algorithms; Biomarkers, Tumor; Breast Neoplasms; Cohort Studies; Estrogen Receptor beta; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Hyperplasia; Immunohistochemistry; Middle Aged; Multivariate Analysis; Risk Factors
PubMed: 26276747
DOI: 10.1158/1940-6207.CAPR-15-0198 -
Microscopy Research and Technique Jan 2001It has recently been shown that the progeny from a single cell may comprise the epithelial population of a fully developed lactating mammary outgrowth in mice. Serial... (Review)
Review
It has recently been shown that the progeny from a single cell may comprise the epithelial population of a fully developed lactating mammary outgrowth in mice. Serial transplantation of epithelial fragments from this clonally derived gland demonstrates that the subsequently generated outgrowths are also comprised of progeny from the original antecedent. All epithelial cell types were found to be present within these clonal normal populations including luminal, myoepithelial, ductal, and lobule-committed epithelial progenitors and fully competent mammary epithelial stem cells. These observations demonstrate the presence of multipotent tissue-specific epithelial stem cells among the parenchyma of the murine mammary gland. Similarly, genetic analysis of contiguous portions of individual human mammary ducts within the same breast indicates their clonal derivation. Here, we discuss the properties, location, division-potential, senescence, and plasticity associated with mammary epithelial stem cells and present the developing evidence for their presence in human breast and their important role in the risk for breast cancer development. Further, we review the present morphologic and genetic evidence for the characterization of specific stem cell markers and lineage-limited progenitor cells in human and rodent mammary epithelium. Microsc. Res. Tech. 52:190-203, 2001. Published 2001 Wiley-Liss, Inc.
Topics: Animals; Breast; Epithelial Cells; Female; Humans; Mammary Glands, Animal; Mice; Morphogenesis; Rats; Stem Cells
PubMed: 11169867
DOI: 10.1002/1097-0029(20010115)52:2<190::AID-JEMT1005>3.0.CO;2-O -
Proceedings (Baylor University. Medical... Jul 2013Mucinous carcinoma of the breast is one of the rarer forms of intramammary cancer, often presenting as a lobulated, fairly well circumscribed mass on mammography,...
Mucinous carcinoma of the breast is one of the rarer forms of intramammary cancer, often presenting as a lobulated, fairly well circumscribed mass on mammography, sonography, and gadolinium-enhanced magnetic resonance imaging. It accounts for 1% to 7% of all breast cancers and generally carries a better prognosis than other types of malignant breast cancers. Metastatic disease occurs at a lower frequency than in other types of invasive carcinoma. We present an atypical case of mucinous carcinoma in a woman who presented with a palpable intramammary lymph node metastasis from an unknown breast primary. Subsequent magnetic resonance imaging and percutaneous biopsy demonstrated histologic findings consistent with a mixed mucinous neoplasm with a micropapillary pattern.
PubMed: 23814397
DOI: 10.1080/08998280.2013.11928989 -
Onkologie 2010Lobular breast cancer in men is an extremely infrequent occurrence due to the lack of lobules and acini in the male breast. Such a rare case is described here. (Review)
Review
BACKGROUND
Lobular breast cancer in men is an extremely infrequent occurrence due to the lack of lobules and acini in the male breast. Such a rare case is described here.
CASE REPORT
A 74-year-old patient presented with a sizeable lesion in the right breast, which proved to be a lobular carcinoma. Genetic studies excluded Klinefelter's syndrome, though revealing an interesting genetic multiformity feature. This case represented a lobular carcinoma in a genotypically male patient under no exogenous or endogenous estrogenic influence.
CONCLUSIONS
The increasing number of male lobular breast cancer cases should be explored more extensively with particular emphasis placed on causally related genetic and hormonal factors.
Topics: Aged; Biopsy, Fine-Needle; Breast; Breast Neoplasms, Male; Carcinoma, Lobular; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Karyotyping; Male; Mastectomy, Modified Radical; Neoplasm Invasiveness; Neoplasm Staging
PubMed: 21124042
DOI: 10.1159/000322224