Abstract PD3-04: Complete pathologic response rate to neoadjuvant chemotherapy increases with increasing HER2 ratio in HER2 over-expressing breast cancer: Analysis of the National cancer database (NCDB)
Authors: Greenwell K , Hussain L , Ho C , Dunki-Jacobs E , Lee D , Bramlage M , Bills G , Mehta A , Jones J , Jackson A , Wexelman B 
Published: February 2018

Background: HER2-positive (HER2+) breast cancer is an aggressive subtype that overexpresses human epidermal growth factor receptor 2 promoting cancer cell growth. Monoclonal antibodies targeting the HER2 receptor have improved survival for this patient population, and current NCCN guidelines recommend consideration of neoadjuvant anti-HER2 therapy (NAC) in Stage 2 & 3 HER2+ breast cancer. Pathologic complete response (pCR) to NAC has correlated with longer disease free survival in multiple trials.

Per ASCO-CAP guidelines tumors are considered HER2+ if HER2 copy number≥ 6/cell, HER2/CEP17 ratio≥ 2, or ratio&lt;2 & HER2 copy number ≥6/cell. We hypothesize that patients with higher HER2 ratios will have higher rates of pCR after NAC.

Methods: The National Cancer Database is supported by the American College of Surgeons and the American Cancer Society containing de-identified patient treatment data from over 1,500 US facilities. We performed a retrospective review comparing pCR rates after NAC based on HER2 ratio. Patients were excluded if they were HER2 negative, did not undergo NAC, or if the HER2 ratio was not recorded. Chi-squared and Fisher's exact test were used to compare pCR versus partial response between deciles of HER2 ratios.

Results: The NCDB included 237,118 patients with HER2 equivocal or HER2+ breast tumors. 29,291 of these patients underwent NAC, and HER2 ratios were recorded in 14,597 of the NAC cases. The majority (98%) of included cases were from 2010-2014. A pCR was noted in 9,752 patients and 11,402 patients had a partial response. No response was observed in 1,735 patients and 6,402 patients had a response but the degree was not recorded.

HER2 ratios were significantly different between pCR vs. partial response groups, p &lt;0.001. We identified a direct relationship between increasing HER2 ratio and response to NAC. For ratios 2-2.9, 23.6% achieved pCR and 44.7% had a partial response. For ratio of 5-5.9, 40.7% achieved pCR and even higher rates of pCR were noted for ratios 8-8.9; 49.5% achieved pCR. While both estrogen receptor (ER) positive and ER negative tumors demonstrated this trend, ER negative tumors had higher rates of pCR (ER negative pCR range 37.6% to 59.4% vs ER positive pCR range 16.9% to 42.3%, p&lt;0.01).

Conclusion: Contrary to current dogma, not all HER2+ tumors respond similarly to NAC. We demonstrate a linear relationship between HER2 ratio and pCR in over 14,000 patients. Those with HER2 ratios ≥5.0 were more likely to achieve pCR compared to patients with ratio ≤4.9. The NCDB reflects current clinical practice across the country not restricted to confines of clinical trials, and in this population higher HER2 ratios are predictive of pCR after NAC.

Response to NAC by Her2 Ratio- Complete vs Partial Response  Response to NAC   p ValueHER2 Ratio Complete Response- pCR (N) Partial Response (N)   1.00- 1.99141819.5%343047.2%&lt;0.01 2.00- 2.9951423.6%97444.7%&lt;0.01 3.00- 3.9928328.7%41942.4%&lt;0.01 4.00- 4.9926533.2%30638.2%&lt;0.01 5.00- 5.9929940.7%24333.1%&lt;0.01 6.00- 6.9929241.0%25435.5%&lt;0.01 7.00- 7.9924746.2%17432.5%&lt;0.01 8.00- 8.9918749.5%12132.0%&lt;0.01 9.00- 9.87 and greater44143.9%31431.3%&lt;0.01TOTAL 394627.0%623542.7%&lt;0.01

Citation Format: Greenwell K, Hussain L, Ho C, Dunki-Jacobs E, Lee D, Bramlage M, Bills G, Mehta A, Jones J, Jackson A, Wexelman B. Complete pathologic response rate to neoadjuvant chemotherapy increases with increasing HER2 ratio in HER2 over-expressing breast cancer: Analysis of the National cancer database (NCDB) [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 PD3-04.