40 Case 1-2020 Answers to the questions
Question 1
Based on the patient’s chief complaint, medical history, and physical examination findings, what initial diagnosis can be suspected?
Answer:
The patient’s chief complaint was a palpable lump in the left breast. She denied associated pain, nipple discharge, or systemic symptoms such as fever or weight loss.
On physical examination, a firm, irregular, and non-tender mass approximately 3 cm in greatest dimension was palpable in the upper outer quadrant of the left breast. There was no palpable axillary lymphadenopathy, and the overlying skin and nipple appeared normal.
Based on these findings, the initial clinical impression was a left breast mass, warranting further imaging and histopathologic evaluation to confirm the diagnosis
Question 2
How does the Oncotype DX 21-gene recurrence score (RS 0–100) influence treatment decisions for a patient with HR-positive, HER2-negative breast cancer? Include how low, intermediate, and high scores guide therapy choices.
Answer:
The Oncotype DX 21-gene assay measures the expression of 21 genes in the tumor and calculates a Recurrence Score (RS) from 0 to 100, which predicts:
Risk of distant recurrence
Potential benefit from chemotherapy¹,⁴
RS Interpretation and Clinical Impact:
RS Range
Risk Level
Typical Recommendation
0–10
Low risk
Endocrine therapy alone; chemotherapy is usually not indicated
11–25
Intermediate risk
Endocrine therapy alone is often sufficient; chemotherapy may be considered if other high-risk features exist (e.g., high tumor grade, large size, high proliferation)
≥26
High risk
Chemotherapy is recommended in addition to endocrine therapy
Patient Application:
This patient has an RS of 24, which falls in the intermediate-risk range. The score suggests a moderate risk of recurrence, supporting endocrine therapy as primary treatment.
Chemotherapy may be considered only if additional clinical or pathological risk factors indicate higher recurrence potential. The Oncotype DX RS helps personalize treatment by identifying patients who may safely avoid chemotherapy while targeting therapy for those at higher risk1,4.
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?
Answer:
The tumor is strongly positive for estrogen receptor (ER) and progesterone receptor (PR), which means it is hormone receptor–positive (HR+). HR-positive tumors depend on hormones like estrogen or progesterone to grow. This makes the cancer likely to respond to endocrine therapy⁵, which works by blocking hormone action or lowering hormone levels.
For postmenopausal women, like this patient, common endocrine therapies include:
Aromatase inhibitors (e.g., anastrozole, letrozole)⁵
Selective estrogen receptor modulators (SERMs) such as tamoxifen⁵
Because the tumor is HR-positive, endocrine therapy is usually the primary treatment, potentially avoiding chemotherapy if other risk factors are low⁵.
Question 4
How is human epidermal growth factor receptor 2 (HER2) status assessed by immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH), and why is it important for treatment planning in early-stage breast cancer?
Answer:
HER2 (human epidermal growth factor receptor 2) is a protein that promotes cell growth. Its overexpression or gene amplification can make the tumor more aggressive5.
IHC (immunohistochemistry): Measures the level of HER2 protein on tumor cells. Results are scored 0 to 3+.
0–1+ → Negative
2+ → Equivocal (uncertain)
3+ → Positive
FISH (fluorescence in situ hybridization): Used if IHC is equivocal⁵. It detects HER2 gene amplification directly in tumor DNA.
Clinical relevance:
HER2-positive tumors respond to HER2-targeted therapies (e.g., trastuzumab, pertuzumab)5, often in combination with chemotherapy.
HER2-negative tumors (like this patient, negative by FISH) do not benefit from HER2-targeted therapy, so treatment focuses on endocrine therapy and possibly chemotherapy based on other risk factors5.
Question 5
Proliferation markers such as Ki-67 are often used in breast cancer evaluation to assess tumor aggressiveness. Although this case report did not include Ki-67 results, what is the clinical significance of proliferation markers, and how could such information complement the immunohistochemistry (IHC) findings if it were available?
Answer:
Proliferation markers, like Ki-67, measure the proportion of tumor cells that are actively dividing, providing insight into tumor growth rate and aggressiveness.
High Ki-67: Indicates rapid tumor growth and a higher likelihood of recurrence, which may support the use of more aggressive treatments such as chemotherapy.
Low Ki-67: Suggests slower tumor growth, consistent with hormone receptor–positive (HR+), HER2-negative tumors, which are often effectively managed with endocrine therapy alone.
Although the Ki-67 index was not reported in this patient’s pathology, including it could have helped further refine risk assessment and treatment decisions when combined with ER, PR, and HER2 status.
In summary, proliferation markers complement standard IHC findings by providing additional prognostic information and guiding therapy selection.
5. Differential Diagnosis
a) Early-stage HR-positive, HER2-negative breast cancer (most likely): Confirmed by histology, immunohistochemistry, and intermediate RS (Spring et al., 2020).
b) HER2-amplified breast cancer: Ruled out by negative FISH testing.
c) Triple-negative breast cancer: Ruled out due to strong ER/PR positivity.
6. Final Diagnosis
The final diagnosis after investigation is Invasive ductal carcinoma of the left breast, clinical prognostic stage IB (T2N0), ER-positive, PR-positive, HER2-negative, grade 2, with an intermediate Oncotype DX 21-gene recurrence score (RS 24).
Treatment initiated was neoadjuvant endocrine therapy, with chemotherapy considered if disease progression occurs or based on additional genomic factors.
