39 Case 1-2020: A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic

Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic.

Spring, L. M., Specht, M. C., Jimenez, R. B., Isakoff, S. J., Wang, G. X., & Ly, A. et al.

2. Case Study Analysis for Initial Diagnosis

Clinical History¹ 

• Age: 62 years old

• Sex: Female

• Ethnicity: Ashkenazi Jewish

Presenting Symptoms¹ 
The patient discovered a palpable mass in her left breast

Medical History¹ 

• Asthma.

• Fibroadenoma of the left breast (excised 30 years ago).

• No family history of breast or ovarian cancer.

• Menarche at 12 years; menopause at 54 years; no hormone replacement therapy.

• She denied pain, nipple discharge, or systemic symptoms.

Drug/Allergies 

• Not specified.

Physical Examination¹ 
A firm mass measuring approximately 3 cm was palpable in the left breast, with no palpable axillary lymphadenopathy.

Investigations¹ 

Figure 1: Imaging Studies of the Breast:
Bilateral mammograms taken in the craniocaudal and mediolateral oblique views (Panels A and B, respectively) reveal a mass in the left breast beneath the skin marker (arrows). On magnified view (Panel C), the lesion appears irregular and spiculated (arrow). Ultrasound imaging (Panel D) demonstrates a solid, irregular mass measuring 3.1 × 1.5 × 1.2 cm. An image obtained during an ultrasound-guided core-needle biopsy (Panel E) shows the needle accurately positioned within the mass.

Imaging Studies¹ 

• Mammography: Irregular mass with spiculated margins in the left breast (Figures 1A-C).

• Ultrasound: Solid, irregular mass 3.1 × 1.5 × 1.2 cm; normal left axillary lymph nodes (Figure 1D).

• Core-needle biopsy: Tissue obtained for histology and immunohistochemistry. Performed under ultrasound guidance (Figure 1E).

Table 1:  Pathological Investigations^1,2

Figure 2: Core-Needle Biopsy Specimens of the Breast:
Panel A (H&E staining):

Hematoxylin and eosin staining of the core-needle biopsy specimen shows invasive ductal carcinoma, characterized by irregular nests and cords of malignant epithelial cells infiltrating the fibrous stroma. The tumor cells exhibit pleomorphic nuclei, increased nuclear-to-cytoplasmic ratio, and mitotic activity, confirming their malignant nature.

Panel B (IHC staining):

Immunohistochemical staining demonstrates strong, diffuse nuclear positivity for both estrogen receptors (ER) and progesterone receptors (PR). Tumor cell nuclei appear brown due to chromogenic staining (DAB), indicating positive receptor expression, while surrounding non-tumor stromal cells remain blue with hematoxylin counterstaining, confirming hormone receptor–positivity (HR+).

3. Clinical Assay Design and Testing 

Principles of Oncotype DX 21-Gene Assay¹²

The Oncotype DX assay evaluates the expression of 21 genes (16 cancer-related and 5 reference genes) in tumor tissue using reverse transcription polymerase chain reaction (RT-PCR). The results are combined into a recurrence score (RS) ranging from 0 to 100. The RS predicts the risk of distant recurrence and potential chemotherapy benefit.

Test Procedure 

1. Sample Preparation: RNA is extracted from formalin-fixed, paraffin-embedded tumor tissue obtained via core-needle biopsy.

1. RT-PCR Quantification: Expression levels of the 21 genes are measured.

1. Recurrence Score Calculation: Expression levels of cancer-related genes are normalized to reference genes; weighted coefficients generate the RS.

Clinical Interpretation² 

• RS 0–10: Low risk; chemotherapy generally not indicated.

• RS 11–25: Intermediate risk; chemotherapy may be omitted in postmenopausal women.

• RS ≥26: High risk; chemotherapy recommended.

Proliferation Markers (e.g., Ki-67) 

• Ki-67 measures actively dividing tumor cells.

• High Ki-67: Rapid tumor growth, higher recurrence risk, may support chemotherapy.

• Low Ki-67: Slower growth, often HR+, HER2-negative; endocrine therapy sufficient.

• Though not reported here, Ki-67 complements ER/PR/HER2 data for therapy decisions¹,4

Quality Control Factors 

• Standardized procedures ensure reproducibility across laboratories.

• High sensitivity and specificity for HR-positive, HER2-negative tumors.

Knowledge Gaps 

• Limited long-term outcomes for postmenopausal women with intermediate RS1.

• Emerging evidence supports neoadjuvant use, but data are still limited2

Table 2: TNM Staging System for Breast Cancer³

Question 3 

 Based on the Immunohistochemistry results, what is the hormone receptor (HR) status of the tumor, and how does it influence the choice of endocrine therapy?