Correlation between Ultrasound Findings and Molecular Subtypes of Breast Cancer

*Eman Soliman Metwally, Rahma Mohammed Abed Alghazal and Ah Haggaa Ali*

#### **Abstract**

Breast cancer is the most common malignant tumor and the major cause of death among women worldwide. Molecular subtyping of breast cancer is important to individualize its management, to understand prognosis of disease and avoid overtreatment. The current study aimed at correlating the breast cancer subtypes with their different ultrasound criteria. The ultrasound findings might have an important role in predicting different groups. The current study is a retrospective study. Which was conducted on 40 females patients with breast cancer; during the period from November 2020 till March 2021.The age were 45–65 years old. They were presented to the Radiology Department, Ain-Shams University, Faculty of Medicine. The selected cases had been afforded from: the Breast-unit of General Surgery Hospital, El Demerdash University Hospital, Clinical Oncology & Nuclear Medicine Department. When analyzing the main four breast cancer subtypes in the current work we found that the rates of Luminal A was 34%, Luminal B was 40%, HER2 was 15%, and TNBC was 11%. LA subtype was strongly associated with hypoechoic lesions showing irregular shape, speculated margin surrounded by desmoplastic reaction with posterior shadowing. LB subtype was associated with irregular shape and speculated margin with absence of desmoplastic reaction. Human Epidermal Growth Factor (HER2) subtype in the current study was found to be associated with irregular shape, lobulated margin, absent desmoplastic reaction with posterior acoustic mixed shadowing and enhancement. This could be related to suspicious microcalcifications. Triple Negative Breast Cancer (TNBC) lesions in the present work were predominantly oval in shape with• circumscribed margin; the benign looking malignant lesions which carry the worst prognosis. Based on the latter finding, the good radiologist should be aware about ultround features of different molecular subtype in order not to under diagnose a malignant breast lesion. The sonographic features as margin, shape, posterior acoustic features were significantly associated with molecular subtypes. The histopathological grade and hormone receptor status. Being able to predict the molecular subtype. The current study recommend that the radiologist should be aware about different imaging features of different molecular subtypes especially the triple negative breast cancer which had the most benign looking criteria aiming for better lesion characterization and to allow the patient to benefit from earlier noninvasive, cheap diagnosis and the curable on time treatment.

**Keywords:** breast cancer, ultrasound features, molecular subtypes

## **1. Introduction**

Cancer Breast is a heterogeneous and complex disease with different morphologic, biologic, and molecular features. The histopathological characteristics of tumors had been used to determine the management of breast cancer. However They do not provide sufficient information due to tumor heterogeneity [1–3].

Distinct molecular subtypes of breast cancer had been defined based on gene expression. Molecular subtyping of breast cancer is essential to individualize its management, to understand prognosis of disease and avoid overtreatment [4].

Ultrasonographic imaging features of breast cancer, including the tumor shape, margin, boundaries, posterior features, multiplicity, orientation, and calcification, are significant predictive sonographic signs of different molecular subtypes [5].

Previous literatures had indicated an excellent improvement in U/S technologies. It would be possible to have highly sensitive machines be able to differentiate malignant solid breast masses from benign ones based on their different U/S criteria [6].

Many studies correlated the ultrasonography features of malignant lesions with their grade, while limited studies discussed the correlation with molecular subtypes of breast cancer. Overlap of benign and malignant ultrasound morphology descriptors still represents a challenge to breast imaging radiologists. Knowing the descriptors of the different molecular subtypes may help radiologists to decrease both false positive and false negative diagnosis [3–6].

#### **2. Aim of the work**

The present study aimed at detecting the correlation between ultrasound morphological features and different molecular subtypes of breast cancer which could increase the diagnostic ultrasound accuracy.

#### **3. Patients and methods**

The current study is a retrospective study. Which was conducted on females patients with breast cancer. They were presented to the Radiology Department, Ain-Shams University, Faculty of Medicine. The selected cases had been afforded from: The Breast-unit of General Surgery Hospital, El Demerdash University Hospital, Clinical Oncology & Nuclear Medicine Department.


*Correlation between Ultrasound Findings and Molecular Subtypes of Breast Cancer DOI: http://dx.doi.org/10.5772/intechopen.108812*

An informed consent explaining the procedure details was obtained from all patients prior to inclusion in this study. The study was conducted according to the stipulations of the ASU ethical and scientific committee. The privacy of participants and confidentiality of data were guaranteed during the various phases of the study. The inclusion criteria were: Female patients with breast cancer, only. The exclusion Criteria were: a) History of neoadjuvant therapy; b) Ductal carcinoma in situ; c) Patients had started any local or systemic therapy.

#### **3.1 Study methods**

Forty female patients had breast cancers were selected for the present study the inpatient wards as well as outpatient clinic were admitted for bilateral Sonomammographic examination. An U/S device; GE (Pristima), Siemens (Mammomat 1000) & Samsung (Accuvix XG) machines in Ain Shams University Medical Hospital. A linear probe of 9–15 MHz was used.

The technique was done after exposure of the breast with the patient lying supine and her ipsilateral hand raised above the head the UIS probe was oriented perpendicular to the chest wall. Radial scanning technique, in a clockwise fashion wising the nipple as a center point wall followed. Scanning of each breast quadrant in the sagittal and transverse planers were performed. Scanning axially lymph nodes.

The examination time took about 20 minutes. All the real-time scanning was performed by a radiologist with at least 5 years of experience in breast U/S. More experienced radiologist with at least 7–10 years' experience rechecked the findings. As a way of a double-blind analysis. The final interpretation and diagnosis were obtained.

#### **3.2 Histopathologic diagnosis, image analysis and interpretation of conventional ultrasound**

U/S guided biopsy was scheduled for patients with suspicious breast lesions. The procedure was performed by at least 7–10 years experienced radiologist. Biopsy was taken under complete aseptic condition. Sterilization of the area of interest with betadine was done; the latter was followed by sterilization the U/S probe. The radiologist used sterile gloves and injected a local anesthesia followed by introduction of the Tru-cut needle. The needle under ultrasound guidance targeted the lesion. At least four core biopsies were taken.

Tissues biopsied were sent to the Pathology Department. The tissues were formalin fixed, paraffin embedded and subsequently used for IHC staining with appropriate antibodies to detect the hormonal status of the lesions (ER, PR, HER2 gene expression and Ki-67). The cutoff point for ER positive, PR-positive expression was 10%. HER-2 status was graded as 0, 1+, 2+ and 3+. The HER-2 status of 3+ was deemed to be positive, while statuses of O and 1+ were deemed to be negative. Fluorescence in situ hybridization (FISH) was performed on all grade 2 samples. Samples with a > 2-froldchange in expression were regarded as negative. Samples with a < 2-fold increase were regarded as positive for gene amplification. Ki67 was visually scored for the percentage of tumor cell nuclei with positive immunostaining above background. Over **Histopathologic diagnosis** by following and receiving the pathology report from the patient.
