Aberrant Breast Research Articles

Anatomy of the human mammary gland: Current status of knowledge

Mammary glands are unique to mammals, with the specific function of synthesizing, secreting, and delivering milk to the newborn. Given this function, it is only during a pregnancy/lactation cycle that the gland reaches a mature developmental state via hormonal influences at the cellular level that effect drastic modifications in the micro- and macro-anatomy of the gland, resulting in remodeling of the gland into a milk-secretory organ. Pubertal and post-pubertal development of the breast in females aids in preparing it to assume a functional state during pregnancy and lactation. Remarkably, this organ has the capacity to regress to a resting state upon cessation of lactation, and then undergo the same cycle of expansion and regression again in subsequent pregnancies during reproductive life. This plasticity suggests tight hormonal regulation, which is paramount for the normal function of the gland. This review presents the current status of knowledge of the normal macro- and micro-anatomy of the human mammary gland and the distinct changes it undergoes during the key developmental stages that characterize it, from embryonic life through to post-menopausal age. In addition, it discusses recent advances in our understanding of the normal function of the breast during lactation, with special reference to breastmilk, its composition, and how it can be utilized as a tool to advance knowledge on normal and aberrant breast development and function. Finally, anatomical and molecular traits associated with aberrant expansion of the breast are discussed to set the basis for future comparisons that may illuminate the origin of breast cancer.

Stromal biomarkers in breast cancer development and progression

Breast cancer is a heterogeneous, multi-factorial disease of aberrant breast development whose etiology relies upon several microenvironmental changes within the tissue. Within the last decade, it has become widely accepted that tumor cells frequently rely on signals from an activated microenvironment in order to proliferate and survive within a tissue. This activated tissue microenvironment involves the appearance of αSMA + fibroblasts (referred to as "cancer associated fibroblasts"), the recruitment of various immune cells (macrophages, T cells, B cells, T regulatory cells), enhanced collagen I deposition, and epigenetic modifications of stromal cells. These stromal changes can predict patient survival and correlate with distinct breast tumor subtypes. Characterizing these stromal changes will facilitate their use as clinical biomarkers in breast cancer, and may facilitate their use as potential drug targets for adjuvant breast cancer therapy.

Aberrant Breast in a Rare Site: A Case Report

Aberrant breast tissue is an anomaly in the embryogenesis of the breast that is found along the mammary ridge or out of that line. We report a case of a 71-year-old female patient with an abdominal aberrant breast tissue found incidentally in a piece of mesenteric biopsy. The histological features were consistent with breast tissue.

NSP 5a3a’s link to nuclear-cyto proteins B23 and hnRNP-L between normal and aberrant breast cell lines

NSP 5a3a had been identified along with three other distinct though similar isoforms corresponding to locus HCMOGT-1 on chromosome 17p11.2.1 Secondary structure analysis of the NSP isoforms revealed similiarity to Spectrin and Spectrin like proteins containing coiled coil domains.1 These proteins have been implicated and found to be involved in a plethora of cellular activities ranging from intracellular trafficking, cellular and subcellular integrity 2, 3 to being involved in protein-protein interactions with other structural proteins as well as involved in protein complex stabilization and scaffolding thus facilitating homo or hetero dimerization of protein complexes.4 The NSP 5a3a isoform had been identified to be highly expressed in-vitro in particular cancer cell lines while very low to null in normal body tissues.1 Subsequent investigation of this isoform revealed its novel interaction with B23 5, a known nucleolar protein involved in ribosome biogenesis, rRNA transcription, mitosis, cell growth control, and apoptosis.6 We have since then, further elucidated its potential involvement in cellular processes such as ribosome biogenesis and rRNA processing by confirming and establishing NSP 5a3a's novel interaction with B23 and ribonuclear protein hnRNP-L, respectively thus possibly implicating NSP 5a3a in cellular processes such as ribosome biogenesis and rRNA transcription . Finally, an intriguing differential cooperation between these proteins has been observed in both normal and cancer breast cell models and additionally through siRNa silencing, we have found hnRNP-L as a potential novel regulator of NSP 5a3a.

HoxC6 regulation of early mammary epithelial growth and differentiation: implications for breast cancer potential.

Abstract Abstract #2010 Background: Early menarche and breast development are increasingly common risk factors for breast cancer. Epigenetic mechanisms implicated include natural and anthropogenic steroids, such as estrogens, that disrupt endocrine signaling and dysregulate stem cell homeostasis. Animal models show that, although a proliferative response to estrogens in mammary epithelium is not observed until near puberty, in utero or neonatal exposure can recapitulate aberrant breast development. The molecular basis for the delay in proliferative response remains poorly understood and assessments of agent activity, potency and risk remain inaccurate. Here, we provide a candidate molecular mechanism involving the homeobox transcription factor HoxC6, through which more accurate assessments may be facilitated.
 Materials & Methods: Genetically and hormonally manipulated in vivo mouse models (HoxC6 targeted disruption, C6KO; and mammary epithelial-specific inducible HoxC6, MMTV-rtTA TRE-HoxC6-IRES-EGFP) and in vitro human breast cancer cell lines (MCF10A, MCF7 and MDA-MB-231; "231") were used to assess impacts on mammary epithelial growth, differentiation and expression of HoxC6 and its direct target genes IGFBP3, CD44 and FGFR2. Cell lines were manipulated using HoxC6 shRNA and cDNA lentivirus and activated Akt isoform retroviral expression vectors. Gene expression and signaling were measured by quantitative RT-qPCR, IHC, Western blot and using the BioPlex200 Multiplex System.
 Results: RT-qPCR analysis shows HoxC6 expression elevated in well-differentiated cell lines (MCF10A, 5.06X; MCF7, 5.16X) and decreased in more aggressive tumor cell lines (-1.95X, 231 cells; relative to A549 cells). HoxC6 knockdown in MCF10A cells results in an inhibition of cellular growth and decreased branching in 3D cultures and dysregulation of HoxC6 target genes. These results are consistent with in vivo results in which C6KO causes defective postnatal mammary epithelial growth/branching. Rescue of growth defects in knockdown MCF10A cells is achieved to varying extents with myristoylated Akt isoforms, however morphological defects persist and are associated with EMT. HoxC6 induction in stem cells is associated with altered self-renewal and differentiation. HoxC6 repression by estrogens was assessed in vivo under conditions of neonatal estrogen exposure and estrogen-free diets, showing alterations in HoxC6 and target gene expressions and other phenotypic changes.
 Discussion: Based on our results, we will present a model in which HoxC6 is estrogen-responsive and coordinates mammary stem/progenitor cell homeostatic pathways, including FGF and GH-IGF1 signaling in the control of pool size and branching morphogenesis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2010.

Primary Infiltrating Ductal Carcinoma Arising in Aberrant Breast Tissue of the Axilla: A Rare Entity. Report of a Case

A 52-year-old woman presented with a palpable nodule in the right axilla. Physical examination revealed a 2.5 x 2.5 cm, nontender, firm, brownish, and peripherally hyperemic mass with overlying skin retraction on the right anterior axillary fold. Bilateral mammogram was negative. Ultrasonography of the right axillary region showed a 1.8 x 1.1 cm, poorly defined hypoechoic mass with irregular margins and posterior acoustic shadowing. Fine-needle aspiration biopsy of the mass revealed malignant epithelial cells. The patient underwent a wide local excision of the right axillary lesion with en bloc axillary lymph node dissection. Histopathological examination revealed an infiltrating ductal carcinoma. Here we report this case of carcinoma originating from aberrant breast tissue in the axilla. It is suggested that subcutaneous lesions of uncertain origin around the periphery of the breast should be suspected for breast carcinoma and treated appropriately.

Different Mutant/Wild-Type p53 Combinations Cause a Spectrum of Increased Invasive Potential in Nonmalignant Immortalized Human Mammary Epithelial Cells

Aberrations of p53 occur in most, if not all, human cancers. In breast cancer, p53 mutation is the most common genetic defect related to a single gene. Immortalized human mammary epithelial cells resemble the earliest forms of aberrant breast tissue growth but do not express many malignancy-associated phenotypes. We created a model of human mammary epithelial tumorigenesis by infecting hTERT-HME1 immortalized human mammary epithelial cells expressing wild-type p53 with four different mutant p53 constructs to determine the role of p53 mutation on the evolution of tumor phenotypes. We demonstrate that different mutant/wild-type p53 heterozygous models generate loss of function, dominant negative activity, and a spectrum of gain of function activities that induce varying degrees of invasive potential. We suggest that this model can be used to elucidate changes that occur in early stages of human mammary epithelial tumorigenesis. These changes may constitute novel biomarkers or reveal novel treatment modalities that could inhibit progression from primary to metastatic breast disease.

Carcinoma Originating from Aberrant Breast Tissue. A Case Report and Review of the Literature

Carcinoma arising from ectopic breast tissue, either supernumerary breast or aberrant breast tissue, is extremely rare. Carcinoma occurs more frequently in the ectopic breast tissue of the axilla than in extra-axillary ectopic breast tissue. Here we report a case of an invasive lobular carcinoma arising from extra-axillary ectopic breast tissue and presenting as a subcutaneous nodule.

Aberrant Breast Cancer

Two female patients with ages 38 and 41 were referred to the breast surgery units with firm inflammatory masses in the axilla. Both of them were treated with antibiotics. In our physical examination, the first patient had a 1 · 1 cm mass at the upper medial quadrant and another conglomerate mass at the axilla. The bilateral mammographic examination showed no evidence of malignity (B_IRADS 2) (Fig. 1). Ultrasonography (USG) of the left breast showed a complicated cyst at the radius of 9 and two hypoecoic benign masses in the axilla, 25 · 17 mm and 17 · 17 mm in size (Fig. 2). In the physical examination of the second patient, we determined a conglomerate mass at the axilla adjacent to the arm. The bilateral mammographic examination showed no evidence of malignity (B_IRADS 2) (Fig. 3). USG of the left breast showed an 31 · 15 mm hypoecoic benign mass in the left axilla. We performed true-cut biopsies to the axillary masses. The pathology evaluation reported invasive ductal carcinoma for both of the patients. The other laboratory and radiologic results indicated that these lesions were not metastatic but primary lesions. To obtain long-term survival, diagnostic suspicion and early biopsy of unidentified lesions of the axilla is essential. Even if radiologically benign, subcutaneous nodules with unknown origin around the periphery of the breast should be always evaluated carefully with the suspicion of carcinoma of aberrant breast tissue. Figure 1. Left axilla with no evidence of malignity.

Bilateral aberrant axillary breast tissue mimicking lipomas: report of a case and review of the literature

A 31 year old Indian woman presented with bilateral axillary masses that became noticeable with the onset of puberty. The masses exhibited similar consistency to the adjacent normal breast tissue but lacked an associated nipple complex. The clinical impression was lipoma; however, mammography, ultrasonography and skin biopsy revealed ectopic breast tissue. These findings were consistent with the diagnosis of aberrant breast tissue. A subset of ectopic mammary tissue, aberrant breast tissue may constitute a diagnostic challenge and is often misdiagnosed as lipoma, hidradenitis, follicular cyst, or lymphadenopathy. In addition, some studies have suggested that aberrant breast tissue may be at higher risk of malignant degeneration. Therefore, it's important that physicians be familiar with this condition as this may contribute to the early detection of ectopic breast cancer.

Carcinoma of aberrant breast tissue. A report of 3 cases.

Abstract Three cases of carcinoma of aberrant breast tissue are described and the literature is briefly reviewed. It is suggested that subcutaneous nodules of uncertain origin around the periphery of the breast should be viewed with suspicion and treated by early excision.

Carcinoma mamario en tejido mamario ectópico: Caso clínico

Ectopic breast tissue, that includes supernumerary breasts and aberrant breast tissue, develops along the mammary line. Malignancies rarely develop in this tissue. We report a 44 years old female subjected to a resection of a 3 cm Ø tumor located 2 cm below the right lower mammary sulcus. The pathological study reported an infiltrating ductal carcinoma. The patient was operated again and a metastatic carcinoma was detected in three resected axillary lymph nodes. Adjuvant chemotherapy and radiotherapy was indicated.

Breast-feeding With Ectopic Axillary Breast Tissue

Breast-feeding With Ectopic Axillary Breast Tissue

Carcinoma of the axillary breast

Axillary breast is one of the varieties of polymastia which is characterized by the presence of more than 2 breasts. It may cause symptoms during pregnancy, lactation, or in the premenopausal period. Unless there are obvious symptoms of lactation or the assistance of further imaging studies such as mammography and breast ultrasound, the diagnosis is often confused with subcutaneous lipoma. The incidence of axillary breast cancer is low but it should be investigated and treated properly in view of another breast cancer in the embryonic milk-line. In this paper we reviewed 4 cases of axillary breast cancer and documented some articles regarding aberrant breast and carcinoma arising from it. It is suggested that subcutaneous nodules of uncertain origin around the periphery of the breast should be viewed with suspicion and treated properly.

Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.

As inherited germ line mutations, such as loss of BRCA1 or AT, account for less than 5% of all breast cancer, most cases involve acquired somatic perturbations. Cumulative lifetime exposure to bioavailable estradiol links most known risk factors (except radiation) for breast cancer. Based on a series of recent experimental and epidemiologic findings, we hypothesize that the multistep process of breast carcinogenesis results from exposure to endogenous or exogenous hormones, including phytoestrogens that directly or indirectly alter estrogen metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal production; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure. As for genetic paths, xenohormones can modify DNA structure or function. As for hormonal paths, two distinct mechanisms can influence the potential for aberrant cell growth: compounds can directly bind with endogenous hormone or growth factor receptors affecting cell proliferation or compounds can modify breast cell proliferation altering the formation of hormone metabolites that influence epithelial-stromal interaction and growth regulation. Beneficial xenohormones, such as indole-3-carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell proliferation, and influence the rate of DNA repair or apoptosis and thereby influence the genetic or hormonal microenvironments. Upon validation with appropriate in vitro and in vivo studies, biologic markers of the risk for breast cancer, such as hormone metabolites, total bioavailable estradiol, and free radical generators can enhance cancer detection and prevention.

Accessory Breast Cancer: A Case Report of Carcinoma Originating from Aberrant Breast Tissue in the Axillar Region.

A 74 year-old woman with accessory breast cancer in the left axillar region had a painful mass in the left axillar region. Physical examination revealed a mass of about 3 cm in diameter with hemorrhagic ulceration of the skin. The movements of her left arm were severely limited because of the pain. A biopsy specimen showed malignant metastatic tissues, whereas the gallium scintigram and bone scintigram disclosed multiple systemic metastases. Though radical cure could not be achieved surgically, she underwent local resection of the left axillar mass to alleviate the clinical symptoms. The histopathological examinaton revealed a solid tubular adenocarcinoma combined with scirrhous type adnocarcinoma, which was compatible with that of breast cancer. Her clinical symptoms were remarkably improved after operation and then she was followed up at the outpatient clinic. However, she died of respiratory failure due to pleural metastases 10 months after operation.

Axillary Breast Tissue

Aberrant breast tissue is usually present along the milk line above or below the normal breast location. Occasionally, it is found in unusual locations, such as the axilla, scapula, thigh, and labia majora. Accessory axillary breast tissue is present in approximately 2% to 6% of women. Although this finding has been reported in a variety of clinical journals, such as Radiology and Human Pathology, it has received little attention in the plastic surgery literature. Axillary breast tissue, presenting as palpable thickenings in the axilla, can undergo monthly premenstrual changes, such as tenderness and swelling, difficulty with shoulder range of motion, and irritation from clothing. These symptoms may be exacerbated and become more apparent during puberty and pregnancy. In addition, it is cosmetically unsightful, and consequently, patients often desire surgery for improvement. We present a study of 28 patients who underwent surgical removal of their axillary breast tissue. From these successful reports, we recommend that axillary breast tissue should be surgically removed.

Ectopic breast cancer: case report and literature review

Ectopic breast tissue includes both supernumerary and aberrant breast tissue. The incidence of supernumerary tissue has been reported as high as 6% depending on the ethnic group studied. The incidence of aberrant breast tissue remains unknown. The development of malignancy within these anomalies is rare. In the following paper, the case report of a patient with an ectopic breast cancer and a second primary cancer of the left anatomic breast is described. A review of the world literature on ectopic breast cancer follows. Specific characteristics of ectopic breast cancer are defined and recommendations for management are made.

Aberrant breast tissue of the perineum: a report on two cases

In this abstract we report on two cases of aberrant breast tissue of the perineum in a 41-year-old and a 42-year-old woman with the complaint of a slowly growing vulvar mass. The masses were not fixed, they were ovoid, rubbery firm and measured 3 x 2.5 and 4 x 3 cm in size. Microscopically, they revealed normal lobular architecture with focal papillomatosis in the former.

Spectrum of diseases in the axilla: A histopathological analysis of axillary masses

Background: This is an analysis of axillary masses to determine the spectrum of diseases that are commonly encountered in the axilla. Materials and Methods: Ten years' consecutive analysis axillary biopsies sent to the pathology laboratory of a tertiary hospital were formalin fixed, paraffin embedded, and stained with hematoxylin and eosin (H and E). Stains such as Ziehl–Neelsen, vermentin and CD5, CD20, and CD23 were also employed in further differentiation of diseases. Results: Fifty-nine axillary lesions were analyzed from 21 males and 38 females. The ages ranged from 2 months to 80 years and peaked in the third decade of life. There were eight developmental (congenital) lesions (13.6%), seven infectious (12.0%), 12 reactive (20.3%), and 31 neoplastic lesions (52.5%). All the congenital lesions were aberrant breast tissues. There were 19 non-neoplastic lymph nodes and 12 of them (63.2%) were reactive hyperplasia remaining (35%) being granulomatous inflammations of which four were tuberculous. A case of hematoma in a 2-month-old male child was seen. The neoplastic diseases were dominated by lipoma; five cases (16.1%), non-Hodgkin's lymphoma; 11 cases (35.5%), and metastatic carcinoma; 5 cases (16.1%). Conclusion: The most common tissue of affectation in the axilla was the lymph node. Malignant neoplastic diseases were the commonest pathology with female predisposition; the peak age of presentation was the third decade of life was the third decade. Histologic evaluation of axillary masses will aid in the prompt and appropriate treatment of diseases to reduce attendant morbidity and mortality.