Breast Disease - Volume 41, issue 1

Authors: Krishnamurthy, Kritika | Deb, Arunima | Alghamdi, Sarah | Schwartz, Michael | Cusnir, Mike | Sriganeshan, Vathany | Poppiti, Robert

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer, one of the leading causes of cancer-related mortality in women worldwide, exhibits wide-ranging histo-morphologic, clinical and molecular diversity. OBJECTIVE: This study compares the genetic alterations of breast tumors with the histo-morphological, hormone receptor status and metastatic “organotropism”. MATERIALS AND METHODS: Twenty-two cases of primary invasive breast carcinoma with local/distant metastasis were retrieved from the pathology archives. The status of estrogen and progesterone receptors by immunohistochemistry was recorded along with other pertinent case data. Next generation sequencing was performed on formalin-fixed paraffin embedded blocks of tumor. RESULTS: The mean age of the …study subjects was 57.9 ± 13.3 years. TP53 mutation was the most common gene alteration in this study and was seen in 40.9% cases. ROS1 gene was mutated in 44.4% PR negative breast cancers while being wild type in the twelve PR positive tumors. (p  = 0.021). STRING interaction network constructed with ROS1 and PR revealed a significantly higher number of interactions in this network than expected (p -value 0.000973). CONCLUSION: This study highlights the significantly higher incidence of ROS1 gene alterations in metastatic PR− breast cancers, with STRING network analysis revealing higher nodal interaction in the nodal network comprised of PR and ROS1 exclusive of ER. Show more

Keywords: Metastatic breast cancer, ER+PR−, TP53, ROS1, STRING network

DOI: 10.3233/BD-220001

Citation: Breast Disease, vol. 41, no. 1, pp. 295-301, 2022

Authors: Shahraki, Zahra | Ghaffari, Mehrangiz | Nakhaie Moghadam, Maryam | Parooie, Fateme | Salarzaei, Morteza

Article Type: Systematic Review

Abstract: INTRODUCTION: Breast cancer is the most common cancer in women worldwide. It is responsible for about 23% of cancer in females in both developed and developing countries. This study aimed to compare the diagnostic performance of contrast-enhanced mammography (CEM) and contrast-enhanced magnetic resonance imaging (CEMRI) in preoperative evaluations of breast lesions. METHODS: We searched for published literature in the English language in MEDLINE via PubMed and EMBASETM via Ovid, The Cochrane Library, and Trip database. For literature published in other languages, we searched national databases (Magiran and SID), KoreaMed, and LILACS. Metadisc1.4 software was used for statistical analysis …RESULTS: A total of 1225 patients were included. The pooled sensitivity of CEM and CEMRI was 0.946 (95% CI, 0.931–0.958) and 0.935 (95% CI, 0.920–0.949), respectively. The pooled specificity of CEM and CEMRI was 0.783 (95% CI, 0.758–0.807) and 0.715 (95% CI, 0.688–0.741), respectively. The sensitivity of CEM was the most in the United States (97%) and the specificity of CEM was the most in Brazil (88%). MRI sensitivity was the most in USA and Egypt (99%) and China had the most MRI specificity (81%) in diagnosis of breast lesions. CONCLUSION: Contrast-enhanced mammography, a combination of high energy image and low energy image, can well display breast lesions and has the diagnostic efficacy equivalent to MRI. Importantly, CEM imaging shows higher specificity, positive predictive value, and diagnostic conformance rate than MRI. Despite some drawbacks such as higher irradiation and iodine usage, CEM has such advantages as convenient and fast examination, strong applicability, and low costs; thus, it can be popularized as a useful tool in breast disease. Show more

Keywords: Contrast enhanced mammography, contrast enhanced magnetic resonance imaging, breast cancer, CEM, CEMRI

DOI: 10.3233/BD-210034

Citation: Breast Disease, vol. 41, no. 1, pp. 303-315, 2022

Authors: Grubstein, Ahuva | Rapson, Yael | Manor, Moran | Yerushalmi, Rinat | Gavrieli, Shlomo | Tamir, Shlomit | Meshulam, Sagit | Atar, Eli | Stemmer, Salomon M. | Shochat, Tzippy | Allweis, Tanir M.

Article Type: Research Article

Abstract: OBJECTIVES: High background parenchymal enhancement (BPE) levels and asymmetric distribution could cause diagnostic uncertainty due to morphological similarity to breast cancer, especially invasive lobular carcinoma (ILC). We investigated BPE in ILC patients, its association with the tumor hormonal profile, and the effect of endocrine treatment (ET). METHODS: The analysis included all MRI examinations performed at our institution between 2010 and 2019 for ILC-diagnosed patients. Baseline study and the first follow-up study were reviewed. Digital medical records were reviewed to retrieve demographics/pathology results/treatment information. BPE and fibroglandular tissue were assessed qualitatively on the contralateral breast according to the criteria …of the Breast Imaging Reporting and Data System (BI-RADS). RESULTS: The study included 129 patients. Most (91%) had pure ILC. All received ET; 12% also received chemotherapy; 90% had surgery first; 70% by breast conservation. On the baseline MRI, 70% had mild or moderate BPE; whereas, on the follow-up study, the majority (59%) had minimal BPE. Most BPE reductions were by 2 degrees. In the baseline study, additional biopsies were required in 59% of cases, and in 17%, a short-term follow-up was recommended. In the follow-up study, biopsies were recommended in 10%, and a short-term follow-up was requested in 16%. A correlation between progesterone receptor intensity index and baseline BPE level was observed (r = 0.3, p = 0.004). CONCLUSION: ILC patients usually exhibit high BPE. ET decreases BPE, and therefore may decrease false-positive interpretations. Additional research is needed to explore whether study can be performed on ET without compromising sensitivity. Key points: ∙ High background parenchymal enhancement levels reduces breast MRI sensitivity, yielding high false positive rates especially when reporting cases of invasive lobular carcinoma [ILC]. ∙Treatment of ILC with endocrine therapy reduces background parenchymal enhancement and thus could decrease these false-positive interpretations. Show more

Keywords: Breast cancer, carcinoma, lobular, MRI scans, retrospective study

DOI: 10.3233/BD-220003

Citation: Breast Disease, vol. 41, no. 1, pp. 317-323, 2022

Authors: Pankratjevaite, Lina | Lind, Katrine | Mele, Marco | Lelkaitis, Giedrius

Article Type: Case Report

Abstract: INTRODUCTION: Breast adenomyoepithelioma is a very uncommon tumor, which is generally considered to be benign, however malignant transformation has been reported. PRESENTATION OF CASE: We report two cases of two women with breast adenomyoepithelioma. CONCLUSION: Diagnosis of adenomyoepithelioma is challenging because tumor may mimic other breast diseases. It has neither specific clinical signs nor radiological features, and the diagnosis is based on histopathological examination of the lesion. The treatment of choice is surgery. The type of surgery depends on the tumor factors and breast size. In malignant cases treatment such as radiotherapy, chemotherapy, immunotherapy may be …used as well. It is very important to give an adequate treatment, otherwise the risk of tumor recurrence, growth or even metastatic spread, when tumor has malignant potential, increases. Show more

Keywords: Adenomyoepithelioma, rare breast disease, surgery, case report

DOI: 10.3233/BD-210077

Citation: Breast Disease, vol. 41, no. 1, pp. 325-330, 2022

Authors: Voutsadakis, Ioannis A.

Article Type: Research Article

Abstract: INTRODUCTION: Losses of genetic material from chromosomes 5q and 16q commonly occur in sub-sets of breast cancer. Their significance from a pathophysiologic point of view is not well-defined. METHODS: This study uses publicly available genomic data from extensive breast cancer datasets to define the landscape of losses in chromosomal arms 5q and 16q in the two sub-types of breast cancer they most commonly occur, basal-like and luminal A cancers, respectively. RESULTS: It is shown that dozens of genes from these chromosomal arms are putatively hemi-deleted in few samples each. No individual gene from either 5q or …16q shows an incidence of deep deletion above 10% in the cohorts with basal-like and luminal A cancers or in the whole cohorts. A few tumor suppressor genes are deleted in a small number of samples, less than 5% in each cohort. Losses of 5q or 16q confer no survival advantage in either the basal-like or the luminal A cohorts from TCGA that harbor them. CONCLUSION: Results suggest that there are no individual genes in chromosomes 5q and 16q whose loss can be implicated in a dominant pathophysiologic sequence of events in breast cancer or its sub-sets. Show more

Keywords: Breast cancer, luminal A, basal-like, chromosome arm loss, aneuploidy, TCGA, METABRIC

DOI: 10.3233/BD-210047

Citation: Breast Disease, vol. 41, no. 1, pp. 331-341, 2022

Authors: Sogunro, Olutayo | Sayyed, Adaah A. | Aminpour, Nathan | Towfighi, Parhom | Maini, Mansi | Masanam, Monika | Deldar, Romina | Murray, Allison | De La Cruz, Lucy | Greenwalt, Ian | Son, Jennifer D.

Article Type: Research Article

Abstract: BACKGROUND: Only 42% of all breast cancer patients undergoing mastectomy elect for breast reconstruction. OBJECTIVE: We evaluate factors impacting complications, recurrence, and mortality in triple-negative breast cancer (TNBC) patients undergoing reconstruction. METHODS: Reconstructive TNBC patients at a single institution from 2010 to 2020 were retrospectively reviewed. Patient demographics, cancer characteristics, reconstruction choice, and complications were collected. Statistical significance was defined at p < 0.05. RESULTS: A total of 131 patients were identified. Average age was 47.8 years, 50.4% were Caucasian and 36.4% were African American. Most patients had invasive ductal carcinoma (90.8%), and …most underwent nipple-sparing (41.2%) or skin-sparing (38.9%) mastectomies. Twenty-one patients (16.0%) experienced postoperative complications. Patients with complications tended to be older (52.1 versus 46.9 years, p = 0.052). At mean follow-up of 52.1 months, 14.5% experienced cancer recurrence and 5.3% died. Deceased patients were significantly younger at diagnosis (42.2 versus 48.5 years, p = 0.008) and had a lower BMI compared to surviving patients (21.2 versus 26.9 kg/m2 ; p = 0.014). Patients younger than age 45 years had higher Ki-67 than those older than 45 years (80.0% versus 60.0%, p = 0.013). Outcomes in autologous- versus implant-based reconstruction were not significantly different. CONCLUSIONS: In TNBC post-mastectomy reconstruction patients, age and BMI were predictors of mortality while race, smoking history, reconstruction choice, or type of implant-based reconstruction had no significant effect on these outcomes. SYNOPSIS: The purpose of this study is to evaluate factors that impact complications, recurrence, and mortality in triple negative breast cancer (TNBC) patients undergoing reconstruction. We identified BMI, neoadjuvant chemotherapy, and age as predictors of complications, recurrence, and mortality in TNBC. Show more

Keywords: Triple negative breast cancer, post-mastectomy reconstruction, recurrence, complications, mortality, autologous-based reconstruction, implant-based reconstruction

DOI: 10.3233/BD-220005

Citation: Breast Disease, vol. 41, no. 1, pp. 343-350, 2022

Authors: Aguiar, David | Ros, Laura | Pérez, Daniel | Croissier, Laura | Mori, Marta | Hernández, María | Vargas, Ana Milena | Galván, Saray | Antonilli, Carla | Saura, Salvador

Article Type: Research Article

Abstract: BACKGROUND: High body mass index (BMI) is regarded as a poor prognostic factor in breast cancer (BC). However, its association with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) remains controversial. OBJECTIVE: We wanted to assess the prognostic impact of BMI in this setting. METHODS: Single-center, retrospective review of 314 BC patients undergoing NAC from 2010 to 2018. Patients were categorized as underweight/normal weight (UW/NW) (BMI < 25) or overweight/obese (OW/OB) (BMI ≥ 25). The relationship between BMI and other traditional clinical-pathological prognostic variables with the pCR rate was investigated using logistic …regression analysis. The effect on event-free survival (EFS) and overall survival (OS) was estimated by the Cox proportional hazards regression analysis. RESULTS: One hundred and twenty-two patients were UW/NW while 192 were OW/OB. Multivariate analysis revealed that hormonal receptors negative, HER2 positive, and clinical tumor stage (cT) 1–2 were independent predictor factors for pCR. Multivariate analysis confirmed tumor grade G3 and lack of pCR as independent adverse prognostic factors for EFS, while factors associated with worse OS were cT3-4, hormone receptors negative, and lack of pCR. Non-significant differences in pCR, EFS, or OS were observed between the two baseline BMI categories. CONCLUSIONS: In our experience, BMI is not associated with pCR, EFS, or OS in BC patients receiving NAC. Achieving pCR is the most consistent factor associated with EFS and OS. Prospective and well-designed studies taking into account other important biological and anthropometric factors are needed to determine the exact role of BMI in this setting. Show more

Keywords: Body mass index, breast cancer, neoadjuvant chemotherapy, obesity, pathological complete response, prognosis, survival

DOI: 10.3233/BD-210071

Citation: Breast Disease, vol. 41, no. 1, pp. 351-361, 2022

Authors: Kharel, Zeni | Nemer, Omar P. | Xi, Wang | Upadhayaya, Bimala | Falkson, Carla I. | O’Regan, Ruth M. | Dhakal, Ajay

Article Type: Correction

DOI: 10.3233/BD-229001

Citation: Breast Disease, vol. 41, no. 1, pp. 363-363, 2022

Authors: Barco, Israel | Chabrera, Carol | García-Fernández, Antonio | Fraile, Manel | Giménez, Nuria | Vallejo, Elena | Zarco, Patricia | González, Sonia | González, Clarisa | Larrañaga, Itziar | Garcia-Font, Marc

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Distant metastatic spread in breast cancer patients is a complex phenomenon involving several prognostic factors. We focused our analysis on early metastatic breast cancer (EMBC) (occurring during the first 36 months) versus late metastatic breast cancer (LMBC) (occurring beyond 3 years) in order to ascertain their possible differential predictive factors. METHODS: diagnostic, surgical, and follow-up data were assessed for consecutive patients with breast cancer undergoing surgery between 1997 and 2019. We analysed the predictive factors for distant metastasis using both univariate and multivariate analysis. RESULTS: The median follow-up for this cohort of 2708 …patients was 89 months. The median metastasis-free interval (FMI) for metastasis patients was 38 months (17 months for EMBC group and 76 months for LMBC group). Distant metastases developed in 12.9% (350/2708); 48% (168/350) of them as EMBC and 52% (182/350) as LMBC. Loco-regional recurrence and nodal extracapsular extension were the only common predictors for both. CONCLUSIONS: EMBC and LMBC appeared as two separate conditions, with a different outcome. In the EMBC group, tumour proliferation related factors were significant (histological grade, tumour size, body mass index), whereas for LMBC, other slow-acting factors seemed to be involved (screening program, tumour burden, bilateral tumour). Show more

Keywords: Breast neoplasms, neoplasm metastasis, early detection of cancer, survival, mortality

DOI: 10.3233/BD-210086

Citation: Breast Disease, vol. 41, no. 1, pp. 365-372, 2022

Authors: Balouchi-Anaraki, Sima | Mohammadsadeghi, Sara | Norouzian, Marzieh | Rasolmali, Reza | Talei, Abdol-Rasoul | Mehdipour, Fereshteh | Ghaderi, Abbas

Article Type: Research Article

Abstract: BACKGROUND: Interleukin-21 (IL-21) is produced by various cell types inducing positive and negative effects in immunity against tumors. OBJECTIVE: To investigate the expression of IL-21 by CD4+ T and IL-21 receptor (IL-21R) by B lymphocytes isolated from breast-tumor draining lymph nodes (TDLNs). METHODS: Fresh lymph node samples were obtained from 45 patients with breast cancer. To assess IL-21 expression, mononuclear cells were briefly stimulated whereas IL-21R expression was assessed in unstimulated B cells. Cells were stained with antibodies for CD4, IL-21, CD19 and IL-21R and acquired by flow cytometry. RESULTS: The frequency of IL-21+ …CD4+ T cells did not show significant association with disease parameters. However, the geometric mean fluorescence intensity (gMFI) of IL-21 in CD4+ T cells was significantly lower in patients with grade III tumor than grade I + II (P  = 0.042). In non-involved LNs, the intensity of IL-21 was significantly higher in patients with stage II compared with stage III (P  = 0.038) and correlated negatively with the number of involved LNs. The frequency of IL-21R+ CD19+ B cells was significantly higher in grade III than grade I + II (P  = 0.037). CONCLUSION: The higher intensity of IL-21 in CD4+ T cells showed association with good prognosticators in breast cancer and warrants further investigation of the role played by IL-21 in immunity against breast cancer. Show more

Keywords: IL-21, IL-21R, tumor draining lymph node, breast cancer

DOI: 10.3233/BD-220013

Citation: Breast Disease, vol. 41, no. 1, pp. 373-382, 2022