Neoadjuvant in Clinical Utility

Neoadjuvant therapy

For some breast cancer patients, neoadjuvant therapy administered before surgery may improve the likelihood of successful breast-conserving surgery through tumor shrinkage, it may downstage the nodal status in the axilla, and help assess primary tumor response to systemic therapy.1

Research results have shown that the Breast Recurrence Score test is a predictor of response to neoadjuvant treatment among post-menopausal, node-negative women and provides useful information to guide systemic treatment decisions:2-7

  • Patients with lower Recurrence Score results experienced greater clinical responses from neoadjuvant hormonal therapy compared to patients with higher Recurrence Score results.
  • Patients with higher Recurrence Score results experienced greater clinical and pathologic responses from neoadjuvant chemotherapy compared to patients with lower Recurrence Score results.

Recurrence Score as a Predictor of Response to Neoadjuvant Chemotherapy

Pease, et al. used the National Cancer Database to identify all patients with T1-T3, ER-positive, HER2-negative primary breast cancer from 2010-2015 who had the Breast Recurrence Score test performed and received neoadjuvant chemotherapy (N=989). Recurrence Score results were strongly associated with the likelihood of pathologic complete response.8

Pathologic Response Rate (pCR)
Pathologic Response Rate (pCR)

Distribution by RS Group:
  • RS 0-17:   23.0%
  • RS 18-30:  45.5%
  • RS 31-100:  31.5%
pCR achieved:
  • 2.2% with RS 0-17
  • 1.6% with RS 18-30
  • 9.6% with RS 31-100, p<0.001

In a similar manner, the National Cancer Database was used to identify all patients with T1-T2, clinically N1/N2, ER-positive, HER2-negative invasive ductal carcinoma of the breast from 2010-2015 who had the Breast Recurrence Score test performed and received neoadjuvant chemotherapy (N=158). Recurrence Score results were significantly associated with the likelihood of pathologic complete response in the axilla.9

Axillary Pathologic Response Rate (pCR)
Axillary Pathologic Response Rate (pCR)

Distribution by RS Group:
  • RS 0-17:   35.4%
  • RS 18-30:  39.2%
  • RS 31-100:  25.3%
Axillary pCR achieved:
  • 10.7% with RS 0-17
  • 9.7% with RS 18-30
  • 27.5% with RS 31-100, p=0.0268

Neoadjuvant Endocrine Therapy and the Breast Recurrence Score Test

TransNEOS Study7

Patients in the TransNEOS study (a translational study of NEOS) had tumors &#ge; 2 cm and archived core-biopsy samples taken before neoadjuvant letrozole and subsequently sent for Breast Recurrence Score® testing. Study endpoints were:

  • Primary - evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS < 18 vs RS ≥ 31
  • Secondary - evaluate clinical response and rate of breast-conserving surgery (BCS) by continuous Recurrence Score result

A total of 295 patients were included in TransNEOS. Recurrence Score group (RS 0-17 vs RS 31-100) was significantly associated with the rate of clinical response (χ2 test, p < .001). With the RS 18-30 group included, Recurrence Score group remained significantly associated with the rate of clinical response (Cochran–Armitage trend test, p < .001)

IMAGE

Clinical Response, n
RS<18
RS 18-30
RS≥31
Total
CR+PR 86 35 12 133
SD 70 46 33 149
PD 1 3 9 13
Total 157 84 54 295
Percent clinical response to neoadjuvant letrozole by Recurrence Score Group (N = 295); CR complete response, PD progressive disease, PR partial response, RS Recurrence Score, SD stable disease

Recurrence Score group was not associated with breast-conserving surgery candidacy before neoadjuvant letrozole but was significantly associated with breast-conserving surgery received after treatment. Among patients with Recurrence Score results 0-17, pre-treatment surgery recommendation significantly differed from post-treatment surgery received (McNemar’s test p < 0.001), whereas there was no significant change among patients with Recurrence Score results 31-100 (p=.075).

Recurrence Score group
No
Yes
p value*
BCS candidacy before neoadjuvant letrozole
RS<18 60 (38%) 97 (62%) 0.878
RS≥31 20 (37%) 34 (63%)
BCS receivedª after neoadjuvant letrozole
RS<18 31 (21%) 118 (79%) 0.009
RS≥31 19 (40%) 29 (60%)
BCS = breast-conserving surgery; RS = Recurrence Score result
*Based on 𝑥2 test.
ªAmong patients with nonmissing information on surgery received.

The authors concluded that the TransNEOS study validates the Recurrence Score result as a significant predictor of clinical response to neoadjuvant letrozole in postmenopausal women with ER+, HER2-negative, clinically node-negative breast cancer. Patients with RS 0-17 were significantly more likely than patients with RS 31-100 to respond to neoadjuvant letrozole and undergo BCS.

Patients with a low Recurrence Score result (0-17) may be candidates for neoadjuvant endocrine therapy to elicit a clinical response and conversion from mastectomy to lumpectomy.

Neoadjuvant Chemotherapy Studies with the Breast Recurrence Score Test

WSG ADAPT Trial

The WSG ADAPT HR+/HER2− trial used clinicopathologic features, Recurrence Score results (static biomarker), and Ki-67 levels after a short course of pre-operative endocrine therapy to assign treatment for patients with HR+, HER2-negative invasive breast cancer to either adjuvant endocrine therapy, or chemotherapy (either in the adjuvant or neoadjuvant setting) followed by adjuvant endocrine therapy.10 For patients who were cN0-1, assignment to chemotherapy was based on one of the following findings: Recurrence Score results 12-25 and Ki-67post-ET > 10% or Recurrence Score results 26-100. Of the 2,241 eligible women assigned chemotherapy in the trial, a total of 864 (including 577 with evaluable Recurrence Score results) received their chemotherapy in the neoadjuvant setting.

Among patients with Recurrence Score results, the rate of pCR was significantly higher in the group with Recurrence Score results 26-100 than with Recurrence Score results 12-25:10

pCR

REFERENCES

  1. ASBS, Performance and Practice Guidelines for the Use of Neoadjuvant Systemic Therapy in the Management of Breast Cancer. 2018.
  2. Gianni et al. J Clin Oncol. 2005.
  3. Ueno et al. Int J Clin Oncol. 2013.
  4. Yardley et al. Breast Cancer Res Treat. 2015.
  5. Bear et al. JSO. 2017.
  6. Robidoux et al. Miami Breast Cancer Conference 2017.
  7. Iwata H, et al. Breast Cancer Res Treat. 2019.
  8. Pease AM, et al. Ann Surg Oncol. 2018.
  9. Pardo et al. Ann Surg Oncol. 2021.
  10. Kuemmel et al. SABCS 2020.

a. DOI: 10.1056/NEJMoa1804710.
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