The "Forgotten" Subtypes of Breast Carcinoma: A Systematic Review of Selected Histological Variants Not Included or Not Recognized as Distinct Entities in the Current World Health Organization Classification of Breast Tumors.

Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis.

Malignant Brenner Tumor of the Ovary: A Systematic Review of the Literature.

BACKGROUND: Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors. METHODS: We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023. RESULTS: After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature. CONCLUSIONS: We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.

Reverse Onco-Cardiology: What Is the Evidence for Breast Cancer? A Systematic Review of the Literature.

Breast cancer and cardiovascular diseases (CVD) represent significant global health challenges, with CVD being the leading cause of mortality and breast cancer, showing a complex pattern of incidence and mortality. We explore the intricate interplay between these two seemingly distinct medical conditions, shedding light on their shared risk factors and potential pathophysiological connections. A specific connection between hypertension (HTN), atrial fibrillation (AF), myocardial infarction (MI), and breast cancer was evaluated. HTN is explored in detail, emphasizing the role of aging, menopause, insulin resistance, and obesity as common factors linking HTN and breast cancer. Moreover, an attempt is made to identify the potential impact of antihypertensive medications and highlight the increased risk of breast cancer among those women, with a focus on potential mechanisms. A summary of key findings underscores the need for a multisystem approach to understanding the relationship between CVD and breast cancer is also explored with a highlight for all the gaps in current research, such as the lack of clinical observational data on MI and breast cancer in humans and the need for studies specifically designed for breast cancer. This paper concludes that there should be a focus on potential clinical applications of further investigation in this field, including personalized prevention and screening strategies for women at risk. Overall, the authors attempt to provide a comprehensive overview of the intricate connections between breast cancer and cardiovascular diseases, emphasizing the importance of further research in this evolving field of cardio-oncology.

Axillary Lymph Node Metastasis from Ovarian Carcinoma: A Systematic Review of the Literature.

BACKGROUND: Axillary lymph node metastasis is a rare stage IV ovarian carcinoma manifestation. This manuscript aims to systematically review the literature regarding axillary lymph node metastasis from ovarian carcinoma. METHODS: We searched three medical internet databases (PubMed, Scopus, and Web of Science) for relevant articles published until 22 July 2023. Cases describing supraclavicular or intramammary lymph node metastases and concurrent metastasis to the breast were excluded. RESULTS: After applying eligibility/inclusion and exclusion criteria, twenty-one manuscripts describing twenty-five cases were included from the English literature. Data were collected and analyzed regarding demographic, clinical, laboratory, radiological, histopathological, and oncological characteristics. CONCLUSIONS: We analyzed the clinical and oncological characteristics of patients with axillary lymph node metastasis from ovarian carcinoma, presented either as an initial diagnosis of the disease or as a recurrent disease. The analysis we performed showed a significant difference only in the serum CA-125 level (p = 0.004) between the two groups. There was no observed difference in womens' survival.

Breast Cancer and Fertility Preservation in Young Female Patients: A Systematic Review of the Literature.

INTRODUCTION: Breast cancer affects almost 1.5 million women worldwide below the age of 45 years each year. Many of these women will be advised to undergo adjuvant chemotherapy to minimize the risk of death or recurrence of the tumor. For these patients, chemotherapy is a known cause of infertility, as it can damage primordial follicles, which can lead to early menopause or premature ovarian insufficiency. This systematic review aims to synthesize the current evidence of the most suitable treatments for fertility preservation. METHODOLOGY: This review was performed following the PRISMA guidelines. The authors conducted an extensive search from the last 15 years. Relevant studies were pursued in PubMed, Embase, and the Cochrane Library up until 31 July 2023. A total of seven eligible studies were identified. RESULTS: From the reviewed literature, ovarian suppression with gonadotropin-releasing hormone agonists showed promising results in preserving fertility for breast cancer patients undergoing chemotherapy. Additionally, oocyte and embryo cryopreservation demonstrated successful outcomes, with embryo cryopreservation being the most effective option. Notably, the slow-freezing and vitrification methods were both effective in preserving embryos, with vitrification showing superior results in clinical-assisted reproductive technologies. Ovarian tissue cryopreservation emerged as a viable option for prepubertal girls and those unable to undergo conventional ovarian stimulation. The potential of in vitro maturation (IVM) as an alternative method presents a promising avenue for future fertility preservation research. DISCUSSION: The most suitable treatments for fertility preservation in young patients is the temporary suppression with luteinizing hormone-releasing analogs, while the patient undergoes chemotherapy and cryopreservation. For cryopreservation, the physicians might deem it necessary to either cryopreserve ovarian tissue taken from the patient before any treatment or cryopreserve embryos/oocytes. Cryopreservation of oocytes and/or embryos is the most effective solution for fertility preservation in women of reproductive age, who have a sufficient ovarian reserve and are diagnosed with breast cancer, regardless of the histological type of the tumor. Because approximately 50% of young breast cancer patients are interested in becoming pregnant right after completion of therapy, the evolution and development of fertility preservation techniques promise to be very exciting.

The Correlation Between Progesterone and Mammographic Density in Postmenopausal Women: A Systematic Review of the Literature and Meta-Analysis.

Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation between estrogen, progesterone, and mammographic density in postmenopausal women and clarify whether these findings are consistent across different types of mammographic breast density. We extracted data concerning mammographic density increases in the populations treated with estrogen-only hormone replacement therapy and those treated with estrogen and progestin hormone replacement therapy. Postmenopausal women treated with estrogen and progesterone regimens had a statistically significant lesser mammographic density increase than estrogen-only hormone replacement therapy regimens.

A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review.

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

Fibroadenoma Arising in Axillary Ectopic Breast Tissue. A Diagnostic Challenge.

Ectopic or accessory breast tissue may occur in primitive embryonic milk lines or locations other than the milk line. The same pathology arising in breast tissue may occur less frequently in ectopic breast tissue. Fibroadenomas rarely occur in ectopic breast tissue, with less than 50 reported cases in the English literature, despite being the most common benign breast neoplasms. Diagnosing fibroadenoma in ectopic breast tissue can be challenging due to the lack of clinical suspicion and the atypical findings in imaging studies. Treatment consists of surgical excision. In this manuscript, we present a case of a 24-year-old patient with a fibroadenoma of the left axilla arising in bilateral axillary ectopic breast tissue, and we comprehensively review the literature.

Effect of Aromatase Inhibitors on Serum Calprotectin Levels in an Animal Experimental Model: Trial.

BACKGROUND/AIM: Utilizing an experimental animal model, we investigated the correlation between aromatase inhibitors (AIs) (anastrozole and letrozole) and Calprotectin levels. AIs have demonstrated superior efficacy when used as adjuvant endocrine therapy or monotherapy for postmenopausal patients with hormone receptor (HR)-positive early-stage breast cancer, although various side effects have been recorded. MATERIALS AND METHODS: Fifty-five adult female Wistar rats were randomized and assigned into four groups. The control group received no intervention. The other three groups were subjected to ovariectomy, and serum Calprotectin levels were measured at baseline, 2, and 4 months. In addition, glucose, total cholesterol, very low-density lipoprotein- (VLDL-) cholesterol, low-density lipoprotein (LDL-) cholesterol, high-density lipoprotein- (HDL-) cholesterol, and triglyceride levels were measured. Histological analysis of liver tissue was carried out following rats' euthanasia. RESULTS: Aromatase inhibitors (anastrozole and letrozole) affect calprotectin levels in ovariectomized rats. Calprotectin, a marker of inflammation, was found to be affected by the use of the inhibitors. CONCLUSION: The potential of hepatotoxicity can be examined by assessing the elevation of inflammation markers such as Calprotectin, which is an indicator that should be strictly taken into consideration when administering aromatase inhibitors as treatment.

Plexiform tumorlet in a woman with postmenopausal endometrioid endometrial carcinoma taking tamoxifen for breast cancer: A case report.

Leiomyomas are the most common benign smooth muscle tumors of the female genital tract. Among the recognized histologic variants, one of the least common is plexiform leiomyoma. When they are small, even microscopic findings, they are referred to as plexiform tumorlets. In this report the authors describe a case of plexiform tumorlet found incidentally in the hysterectomy specimen of a 64-year-old woman with concomitant endometrioid endometrial carcinoma and a previous history of invasive lobular breast carcinoma. The endometrioid endometrial carcinoma arising on a polyps was diagnosed in a curettage specimen. In the hysterectomy specimen there was no residual endometrioid endometrial carcinoma. Six uterine leiomyomas were found. A small (3 mm) well circumscribed tumor was located in the uterine wall. Histologically it consisted of small nests, islands, cords, and tubules of relatively uniform, round to oval cells surrounded by loose stroma. The differential diagnosis was challenging, and included plexiform leiomyoma, uterine tumor resembling ovarian sex cord tumor, endometrial stromal tumor, and poorly differentiated endometrial or metastatic invasive lobular breast carcinoma. After careful morphologic evaluation and appropriate use of immunohistochemical stains the diagnosis of plexiform tumorlet was made.

Local recurrence for phyllodes tumours of the breast: Systematic review and meta-analysis.

The objective of the present systematic review was the determination of methodologies preferable for treating phyllodes tumors (PTs) of the breast and whether the malignancy of the tumor is of significance to the selected treatment. In addition, to investigate if local recurrence (LR) within patients is different based on the therapeutic approach followed by the physician. All studies were gathered by utilization of the biggest online medical databases in the world including PubMed, Cochrane, Embase, Web of Science and Google Scholar. Due to the specificity of the study, the resultant set of studies included in the present analysis was not large. All included studies had to refer to patients diagnosed with PTs of the breast, include the malignancy of the tumor and the preferred treatment. Moreover, they included a reference to LR post-treatment, even if there wasn't any. The age range of patients was 20-55 years old and follow-ups should have been performed. As a result, from the initial 484 studies gathered and after proper and thorough evaluation, only 10 were of significance. The studies appeared heterogeneous in terms of population, topology, treatment methodology, additional therapeutic approaches, LR rate, age and follow-up periods. Overall, excisions were used for non-malignant tumors while mastectomy was preferable for tumors with malignancy. Radiotherapy was used both as an additional treatment for tumors and LR. Also, it was revealed that LR varied based on the malignancy and treatment methodology.

Metaplastic Matrix-Producing Carcinoma and Apocrine Lobular Carcinoma In Situ Associated with Microglandular Adenosis: A Unique Case Report.

Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The glandular structures lack a myoepithelial layer; however, they are surrounded by a basement membrane. Its clinical course is benign, when it is not associated with invasive carcinoma. In around 30% of cases, there is a gradual transition to atypical microglandular adenosis, carcinoma in situ, and invasive breast carcinoma of several different histologic subtypes, including an invasive carcinoma of no special type, metaplastic matrix-producing carcinoma, secretory carcinoma, metaplastic carcinoma with squamous differentiation, acinic cell carcinoma, spindle cell carcinoma, and adenoid cystic carcinoma. Recent molecular studies suggest that microglandular adenosis is a non-obligate precursor of triple-negative breast carcinomas. In this manuscript, we present a unique case of microglandular adenosis associated with metaplastic matrix-producing carcinoma and HER-2 neu oncoprotein positive pleomorphic lobular carcinoma in situ with apocrine differentiation in a 79-year-old patient.

Soy Isoflavones and Breast Cancer Risk: A Meta-analysis.

BACKGROUND/AIM: Soy contains genistein and daidzein isoflavones. Isoflavones are phytoestrogens, with a similarity in structure to human 17-ß estradiol hormone. They imitate the action of estrogen on organs by binding and activating estrogen receptors. Numerous studies have examined the relationship between soy consumption and breast cancer but not the amount of consumption itself. We performed a systematic review of the literature in order to determine whether the amount of soy and isoflavones consumed has a positive effect in pre- and post-menopausal women. MATERIALS AND METHODS: Data gathering was performed following PRISMA guidelines. Narrowing down the result set for all relevant data was performed via title, abstract, full-text evaluation and the snowball procedure. The selected articles had all relevant data extracted. Analysis of the data was performed using Cochrane's Review Manager statistical analysis tool in order to draw conclusions regarding the positive effect for the amount of soy and isoflavones consumed. RESULTS: Significant results were found when statistically analyzing data from prospective studies which compared soy isoflavones consumption, breast cancer risk and occurrence. The data were indicative of a clear inverse correlation between the amount of isoflavones consumed and breast cancer occurrence in pre- and post-menopausal women. CONCLUSION: The consumption of soy isoflavones can reduce the risk of breast cancer in pre-menopausal and post-menopausal women.

Mammary Myofibroblastoma: Report of a Case and Review of the Literature.

Mammary myofibroblastoma is a benign mesenchymal tumor composed of fibroblasts, myofibroblasts, and a variable number of adipocytes. Mammary myofibroblastoma usually occurs in men of older age and is less common in postmenopausal women. It may also happen in extramammary sites along the milk line. In this instance, it is referred to as mammary-type myofibroblastoma. Rarely multifocal and bilateral tumors have been described. Clinically and radiologically, it can be misinterpreted as a malignant tumor due to its rarity. Size usually does not exceed 3 cm. The diagnosis requires clinicopathological correlation with morphological and immunohistochemical evaluation, especially in limited biopsy specimens. We herewith describe a rare case of mammary myofibroblastoma in a 37-year-old female patient. We also review the literature focusing on the potential differential diagnostic issues and discuss this tumor's ultrastructural and cytogenetic findings.

The expression of Galectin-3 in endometrial cancer: a systematic review of the literature.

BACKGROUND: Galectin-3 is part of a protein group called lectins and acts as a multifunctional glycoprotein due to its expression location. Galectin-3 is expressed by different human tissues. It plays a significant role in carcinogenesis and the selection of tumor-related physiological and pathological activities. Galectin-3 has been utilized through the years as a diagnostic and prognostic marker for various types of cancers. METHODS AND RESULTS: This review describes the outcomes of some studies on the matter that were selected appropriately through a review of the existing literature. These studies examined the levels of Galectin-3 expression in endometrial carcinomas, the outcomes, and the prognosis of these carcinomas. Two of the studies concluded that high expression of Galectin-3 is associated with a tumor's histological grade, type and depth. This enhanced nuclear Galectin-3 expression might assist in progression to atypia and neoplasia. The other three on the contrary concluded that malignant tumors had a decreased expression of Galectin-3 and that Galectin-3 played a suppressive role in tumor growth. CONCLUSIONS: The part Galectin-3 might potentially have in metastasis of cancers and the offering of a better prognosis for patients is of high importance. To date, there is minimal literature regarding the effects of Galectin-3 and more research is required.

Dermatofibrosarcoma protuberans of the breast: A case study.

Dermatofibrosarcoma protuberans (DFSP) is a superficial mesenchymal neoplasm that originates from the dermal fibroblasts and tends to be locally aggressive. Although infrequent, it is one of the most common cutaneous sarcomas. It mainly affects young and middle-aged patients 20 to 50 years old. Any area of skin may be involved, but the most common sites of presentation are the trunk and extremities. DFSP of the breast is extremely rare. It classically presents as a nodular, exophytic, cutaneous mass, though initially it can manifest as a flat plague and can show persistent but slow growth for many years. Due to increased risk of local recurrence, the standard of care for localized disease is surgical excision with adequate margins. Wide local excision is the most common technique used, but as an alternative Mohs micrographic surgery has emerged as a procedure that offers lower local recurrence rates. Metastases are rare but have been previously reported. In such patients, treatment with imatinib or radiotherapy can be considered. The current case presents a 52-year-old lady with DFSP of the breast that was successfully managed by the Breast Unit of Athens Medical Center-Psychiko Clinic.

The expression of Galectin-3 in breast cancer and its association with metastatic disease: a systematic review of the literature.

Breast cancer is the most common form of cancer and the second highest cause of cancer mortality in female patients. The significance of the expression of Galectin-3 has been correlated with various malignancy types and in data from several research papers, the expression of Galectin-3 has been associated with the progression and metastasis of breast cancer. In the present study, the authors' goal is to identify whether the expression of Galectin-3 in breast cancer can be associated with the presence and/or recurrence of a metastatic disease. Both Scopus and PubMed databases were utilized, by inputting the following combination of keywords: (((Breast) AND Metastasis)) AND ((Galectin 3) OR Galectin-3). The time of publication and text availability were not considered when searching the databases and all relevant articles in English were initially accepted. We included one case-control study, three retrospective case studies and one retrospective cohort study. In two of the included studies, the levels in concentration of Galectin-3 were not correlated with a significant difference in prognosis. In two studies, the lacking in expression of Galectin-3 was associated with a worse prognosis and in one of the studies selected, the elevated levels of Galectin-3 were correlated with recurrence of disease in triple negative breast cancer cases. For most of the studies selected for this review, the results were contradictory in regard to the role of Galectin-3 for prognosis and metastatic potential in female breast cancer patients. It is still unclear, whether Galectin-3 can be used as a prognostic marker for advanced breast cancer disease.

The expression of galectin-3 in breast cancer and its association with chemoresistance: a systematic review of the literature.

PURPOSE: Galectin-3 is a Mr 31,000 protein that belongs to a family of carbohydrate-binding proteins. Galectin-3 has already been associated with protection against apoptosis through cell to cell or cell to matrix adhesion processes. It seems that galectin-3 plays an important role in tumor progression, cell growth, invasion and metastasis. Galectin-3 is the only member of the chimeric galectins that has an N-terminal glycine and proline domain and a C-terminal carbohydrate recognition domain that allows galectin-3 to accommodate larger structures such us polylactosaminoglycans and intervene to DNA damage repair process. In this systematic review, our primary goal is to identify the effect of galectin-3 expression in association with drug resistance and apoptosis inhibition in breast cancer. MATERIALS AND METHODS: Scopus and PubMed databases were searched on 26 November 2018 using the following combination of keywords: (galectin-3 OR gal-3 OR LGALS3) AND (breast cancer) AND (chemoresistance OR (drug resistance) OR chemosensitivity). All the articles in English, regardless the time of publication, text availability and species included were initially accepted. RESULTS: In the majority of the included studies, the expression of galectin-3 had a protective role in cell survival via different pathways such as the response to DNA damage and repair or the inhibition of apoptosis after treatment with a chemotherapeutic agent. CONCLUSION: Galectin-3 expression in breast tumors might be an important factor in the selection of the most suitable treatment.

Assessment of bone metabolism and biomechanical properties of the femur, following treatment with anastrozole and letrozole in an experimental model of menopause.

The aim of the present study was to investigate the impact of anastrozole and letrozole supplementation following surgically induced menopause on bone metabolism and biomechanical properties. A total of 45 Wistar rats underwent ovariectomy and were then randomly allocated to receive no treatment, anastrozole or letrozole. At 2 and 4 months following the initiation of the present study, the serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined, and the animals were sacrificed at the end of the 4-month period to assess the biomechanical properties of the femoral bones. The applied force and the deflection of the central section were recorded during the test. Taking advantage of these quantities, the fracture force, the stiffness of the bone and the energy absorbed until fracture were determined. At 2 months following the initiation of the experimental protocol, the mean OPG levels were significantly increased in the control group compared with the anastrozole-treated group (P<0.01). Similarly, RANKL levels were significantly increased in the control rats compared with the anastrozole-treated animals (P<0.001) and animals that received letrozole (P<0.05). Notably, these trends were not observed at the end of the experiment (4 months). A biomechanical study of the femoral bones revealed significantly decreased stiffness among animals that received anastrozole (P<0.05) and letrozole (P<0.01) compared with their control counterparts. The results of the present study indicate that treatment with anastrozole and letrozole significantly increases the levels of OPG and RANKL in bone, an effect that appears to be directly associated with the biomechanical properties of bones.

Ulipristal acetate for uterine fibroids: a systematic review and meta-analysis.

Ulipristal acetate (UA), a selective progesterone modulator, has been approved for short-term therapy for symptomatic fibroids. We decided to undertake a systematic review of the best available evidence and draw a more definitive conclusion regarding the efficacy of UA for the management of uterine fibroids. The outcomes included symptomatic relief, quality of life-related parameters, reduction in fibroid size, side effects and recurrence rate. We included four randomised controlled trials which consisted of three trials which compared UA with placebo, and one trial compared it with gonadotropin-releasing hormone analogues for symptomatic relief. The three trials comparing UA with placebo reported significant improvement in symptoms related to excessive uterine bleeding as evidenced by the attainment of amenorrhea or reduction in pictorial blood assessment chart. However, due to the heterogeneity of the available data, a meta-analysis was possible only for one the outcomes - attainment of amenorrhea which indicated improvement in symptoms [57.88 (19.81-169.16); p < 0.00001]. The improved quality of life parameters and reduction in fibroid size was noted in the UA group. With regards to adverse events, even though the three included studies reported increased non-physiological endometrial-related changes following UA, these changes reverted back to normal within 6 months. Short-term use of UA seems to be an effective and safe method of treating uterine fibroids.