Background: Studies using the 21-gene recurrence score (RS) have shown early-stage, low-risk pathologic and genomic breast cancers do not benefit from systemic chemotherapy (CTx) whereas early stage, high-risk breast cancers have improved outcomes when treated with CTx. Data is lacking for patients with discordant risk factors and which feature, genomic or clinical, plays more of a role in determining outcomes.

Methods: A retrospective analysis was conducted to identify early-stage breast cancer patients with discordant features, defined as low-risk genomic/high-risk pathologic factors (LG/HP) or high-risk genomic/low-risk pathologic factors (HG/LP), from August 2011–December 2016. LG/HP breast cancer was defined as a RS <18 with ≥2 high-risk pathologic factors: tumor size (T) ≥2cm, lymph node (N) positivity, or grade 2-3 disease. HG/LP breast cancer was defined as a RS ≥31 with all three low-risk pathologic factors: T <2cm, N negativity, and grade 1-2 disease.

Results: There were 469 patients with low-risk RS identified of whom 118 (25%) met discordant high-risk pathologic criteria and 62 patients with high-risk RS of whom 14 (23%) met discordant low-risk pathologic criteria. Thirty patients in the LG/HP group received CTx despite a low RS. Of the 118 LG/HP patients, there were 22 (19%) breast cancer recurrences; 21 with locoregional and one with metastatic disease. Of the locoregional recurrences, 10 were contralateral breast whereas 11 were in-breast recurrence despite breast conservation therapy. Of the 14 HG/LP discordant patients, of whom 12 received CTx, 3 (21%) had breast cancer recurrence; one with metastatic disease to the lung and the other two with contralateral breast cancer. Majority of all recurrences occurred >5 years after initial diagnosis. Staging and management depicted below.

Management (Mgt) of Discordant Risk Cancers

  LG/HP initial diagnosis (n=118) LG/HP recurrence (n=22) HG/LP initial diagnosis (n=14) HG/LP recurrence (n=3) 
Stage         
0 0 4 0 0 
1A 14 11 14 2 
IB 14 1 0 0 
IIA 56 5 0 0 
IIB 25 0 0 0 
IIIA 2 0 0 0 
IV 0 1 0 1 
Surgical Mgt         
Partial mastectomy 73 7 10 2 
Simple mastectomy 43 14 4 0 
LN Mgt         
Sentinel LN biopsy 85 10 13 2 
Axillary LN dissection 25 3 1 0 
Unknown/Not Applicable 6 8 0 0 
Radiation Mgt         
Yes 81 6 10 3* 
No/Unknown 35 15 0 0 
Hormonal Therapy         
Yes 94 17 14 3 
No/Unknown 24 5 0 0 
Systemic CTx         
Neoadjuvant 6 1 0 0 
Adjuvant 24 2 12 2 
No/Refused 88 19 2 1 
  LG/HP initial diagnosis (n=118) LG/HP recurrence (n=22) HG/LP initial diagnosis (n=14) HG/LP recurrence (n=3) 
Stage         
0 0 4 0 0 
1A 14 11 14 2 
IB 14 1 0 0 
IIA 56 5 0 0 
IIB 25 0 0 0 
IIIA 2 0 0 0 
IV 0 1 0 1 
Surgical Mgt         
Partial mastectomy 73 7 10 2 
Simple mastectomy 43 14 4 0 
LN Mgt         
Sentinel LN biopsy 85 10 13 2 
Axillary LN dissection 25 3 1 0 
Unknown/Not Applicable 6 8 0 0 
Radiation Mgt         
Yes 81 6 10 3* 
No/Unknown 35 15 0 0 
Hormonal Therapy         
Yes 94 17 14 3 
No/Unknown 24 5 0 0 
Systemic CTx         
Neoadjuvant 6 1 0 0 
Adjuvant 24 2 12 2 
No/Refused 88 19 2 1 

*metastatic pt with SBRT to lung

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Conclusions: Using traditional low-risk RS of 18, we observed more than expected recurrences in our LG/HP discordant patients. Thus suggesting, in patients with discordant results, clinicians must consider both pathologic and genomic factors to optimize patient-specific treatment. Further studies are needed to improve the outcomes of this unique patient population.

Citation Format: Blankenship LM, Ezekwudo D, Jaiyesimi I, Stender M, Alassi O, Kresge C, Gaikazian S. Discordant breast cancer: Genomic verse clinicopathologic [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-17.

©2018 American Association for Cancer Research.
2018
American Association for Cancer Research.