What is the significance of ER (Estrogen Receptor) and PR (Progesterone Receptor) status, HER2 (Human Epidermal growth factor Receptor 2) status, aneuploidy, diploidy, and p53 in a patient with Ductal Carcinoma In Situ (DCIS)?

Biomarker Significance in Ductal Carcinoma In Situ (DCIS)

ER/PR Status

For DCIS, ER and PR testing is not routinely recommended for treatment decisions, though it may be considered specifically for tamoxifen candidacy in ER-positive disease. 1

• The American Society of Clinical Oncology states that data are insufficient to recommend routine measurement of ER and PgR for therapy recommendations in DCIS patients who are candidates for hormonal therapy 1
• ER negativity is associated with worse outcomes in DCIS, but it is not an independent predictor when accounting for high nuclear grade and necrosis 1
• The ESMO guidelines suggest adjuvant tamoxifen should be considered in women with ER-positive DCIS, while its use in ER-negative disease may be detrimental 1
• If you choose to test ER/PR in DCIS, use it solely to guide tamoxifen decisions in ER-positive patients after breast-conserving surgery with radiation 1

Common Pitfall to Avoid

Do not use ER status as a prognostic marker to predict outcomes in DCIS—nuclear grade and necrosis are the independent predictors of recurrence risk, not hormone receptor status 1

HER2 Status

HER2 testing is not recommended for routine clinical use in DCIS patients. 1

• Multiple consensus guidelines from the American College of Radiology, American College of Surgeons, College of American Pathologists, and Society of Surgical Oncology explicitly state that oncogene amplification (including HER2) is not necessary for noninvasive breast carcinomas 1
• The 2002 updated standard reaffirms that HER2/neu gene amplification/protein overexpression is not necessary for routine evaluation of noninvasive breast carcinomas 1
• Despite guideline recommendations against routine testing, emerging research suggests HER2-positive DCIS may be associated with adverse clinicopathological parameters, though this has not translated into clinical practice recommendations 2
• Interestingly, research shows HER2-positive DCIS is actually associated with lower risk of invasive breast cancer recurrence compared to HER2-negative DCIS, with curves separating only after 10 years 3

Nuance in the Evidence

While guidelines uniformly recommend against HER2 testing in DCIS, research data show complex associations: HER2 positivity correlates with high grade and ER negativity 3, 4, yet paradoxically predicts lower invasive recurrence risk 3. The ER-positive/PR-negative/HER2-positive pattern specifically predicts higher recurrence rates 5. However, these research findings have not been incorporated into clinical practice guidelines, so HER2 testing remains non-standard 1

Ploidy (Aneuploidy/Diploidy)

DNA content analysis including ploidy determination is not recommended for DCIS. 1

• The 1998 consensus standards explicitly state that determinations of DNA content (ploidy) are not necessary for noninvasive breast carcinomas 1
• The 2007 ASCO update confirms that present data are insufficient to recommend use of DNA content or other flow cytometry-based markers of proliferation to assign patients to prognostic groupings 1
• Research shows aneuploidy is detected in 77.5% of DCIS cases, mainly in high and intermediate grade subtypes (100% and 80% versus 35.7% in low grade), but this has not translated into clinical utility 4

Why This Matters

Although aneuploidy correlates with higher grade DCIS 4, nuclear grade itself is already reported and used for clinical decision-making 1. Adding ploidy analysis provides no additional actionable information beyond what nuclear grading already captures.

p53 Status

p53 testing is not recommended for DCIS. 1

• Consensus guidelines state that oncogene determinations, which would include p53, are not necessary for noninvasive breast carcinomas 1
• Research shows p53 protein expression is detected in 36.8% of DCIS cases, but no relationship exists between p53 expression and histologic subtype or grading of DCIS 4
• Unlike in invasive breast cancer where p53 mutations have prognostic significance, p53 status in DCIS has not demonstrated clinical utility for treatment decisions 4

What Actually Matters for DCIS Management

Focus on these pathologic features that are clinically actionable: 1

• Nuclear grade (low, intermediate, high) 1
• Presence or absence of necrosis 1
• Architectural pattern (comedo, cribriform, micropapillary, papillary, solid) 1
• Extent/size of DCIS 1
• Surgical margin status (most critical factor) 1

These features directly influence decisions about breast-conserving surgery versus mastectomy, need for radiation therapy, and consideration of tamoxifen 1