Loss of HER2‐positivity following neoadjuvant targeted therapy for breast cancer is not associated with inferior oncologic outcomes

Wetzel, Catherine L; Sutton, Thomas L.; Gardiner, Stuart Keith; Farinola, Maryam A.; Johnson, Nathalie; Garreau, Jennifer R.

doi:10.1002/jso.26646

Cited by 11 publications

(17 citation statements)

References 21 publications

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“…In a retrospective cohort study of 348 HER2‐positive breast cancer patients, of which 58.9% received neoadjuvant dual HER2‐targeted treatment, Wetzel et al reported an overall discordance rate of 28%. In patients who received neoadjuvant TCHP, the discordance rate was 34.4%, whereas the discordance rate was 28.1% for patients who received TCH 20 . In addition, Ignatov and colleagues performed a retrospective study of 205 patients with HER2‐positive breast cancer with residual disease—of which 167 received neoadjuvant single‐agent HER2‐targeted therapy and 19 received dual anti‐HER2 treatment—and reported an overall discordance rate of 42% 13 .…”

Section: Discussionmentioning

confidence: 99%

Incidence and prognostic impact of HER2‐positivity loss after dual HER2‐directed neoadjuvant therapy for HER2+ breast cancer

et al. 2023

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Background Loss of HER2 “positivity” can occur in patients with residual disease after neoadjuvant treatment, but the incidence of HER2‐positivity loss after neoadjuvant dual HER2‐targeted treatment plus chemotherapy, the current standard‐of‐care for most early stage HER2‐positive breast cancers, is not well described. Previous studies that report the HER2 discordance rate after neoadjuvant treatment also do not include the novel HER2‐low category. In this retrospective study, we determine the incidence and prognostic impact of HER2‐positivity loss, including the evolution to HER2‐low disease, after neoadjuvant dual HER2‐targeted therapy with chemotherapy. Methods Clinicopathologic data for patients with stage I‐III HER2+ breast cancer diagnosed between 2015 and 2019 were reviewed in this single institution retrospective study. Patients who received dual HER2‐targeted treatment with chemotherapy were included, and HER2 status before and after neoadjuvant therapy was interrogated. Results A total of 163 female patients were included in the analysis with a median age of 50 years. A pathologic complete response (pCR as defined by ypT0/is) was achieved in 102 (62.5%) of 163 evaluable patients. Among the 61 patients with residual disease after neoadjuvant therapy, 36 (59.0%) had HER2‐positive and 25 (41.0%) had HER2‐negative residual disease. Of the 25 patients with HER2‐negative residual disease, 22 (88%) of patients were classified as HER2‐low. After a median follow‐up of 3.3 years, patients who retained HER2‐positivity after neoadjuvant treatment had a 3‐year IDFS rate of 91% (95% CI, 91%–100%), while patients who lost HER2‐positivity had a 3‐year IDFS rate of 82% (95% CI, 67%–100%). Conclusion Almost half of patients with residual disease following neoadjuvant dual HER2‐targeted therapy plus chemotherapy lost HER2‐positivity. The loss of HER2‐positivity may not confer negative prognostic impact, although the results were limited by short follow‐up time. Further research on the HER2 status after neoadjuvant treatment may help guide treatment decisions in the adjuvant setting.

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Section: Discussionmentioning

confidence: 99%

Incidence and prognostic impact of HER2‐positivity loss after dual HER2‐directed neoadjuvant therapy for HER2+ breast cancer

et al. 2023

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“…Studies show that AR can probably predict neoadjuvant treatment effects. AR expression seemed to be related to a lower pCR rate and worse outcome in TNBC [3,[17][18][19][20], but there was also controversy related to these results [21]. In HER2 positive breast cancer, AR+ positivity was associated with pCR, but in this study, only 57.3% of patients received trastuzumab [15].…”

Section: Introductionmentioning

confidence: 80%

“…AR expression has been suggested to predict the response to neoadjuvant therapy in the literature. AR-negative TNBC patients had higher pCR rates than AR-positive TNBC patients [3,[18][19][20]. In these studies, researchers often adopted 1% or 10% as the cutoff of AR.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor: A New Marker to Predict Pathological Complete Response in HER2-Positive Breast Cancer Patients Treated with Trastuzumab Plus Pertuzumab Neoadjuvant Therapy

Zhang

Wang

et al. 2022

JPM

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(1) Background: Neoadjuvant therapy is the main therapeutic strategy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, and the combination of trastuzumab and pertuzumab (HP) has become a routine treatment. How to predict and screen patients who are less likely to respond to neoadjuvant therapy is the focus of research. The androgen receptor (AR) is a biomarker that is widely expressed in all breast cancer subtypes and is probably related to treatment response and prognosis. In this study, we investigated the relationship between AR expression and treatment response in HER2-positive breast cancer patients treated with HP neoadjuvant therapy. (2) Methods: We evaluated early breast cancer patients treated with HP neoadjuvant therapy from Jan. 2019 to Oct. 2020 at Peking University First Hospital Breast Cancer Center. The inclusion criteria were as follows: early HER2-positive breast cancer patients diagnosed by core needle biopsy who underwent both HP neoadjuvant therapy and surgery. We compared the clinical and pathological features between pathological complete response (pCR) and non-pCR patients. (3) Results: We included 44 patients. A total of 90.9% of patients received neoadjuvant therapy of taxanes, carboplatin, trastuzumab and pertuzumab (TCHP), and the total pCR rate was 50%. pCR was negatively related to estrogen receptor (ER) positivity (OR 0.075 [95% confidence interval (CI) 0.008–0.678], p = 0.021) and positively related to high expression levels of AR (OR 33.145 [95% CI 2.803–391.900], p = 0.005). We drew a receiver operating characteristic (ROC) curve to assess the predictive value of AR expression for pCR, and the area under the curve was 0.737 (95% CI 0.585–0.889, p = 0.007). The optimal cutoff of AR for predicting pCR was 85%. (4) Conclusion: AR is a potential marker for the prediction of pCR in HER2-positive breast cancer patients treated with HP neoadjuvant therapy.

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“…In contrast, assessment of gene amplification by ISH is less dependent on technical variables. The ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up of primary breast cancer suggest that HER2 gene amplification status may be determined directly from all invasive tumors using any type of in situ hybridization (fluorescent, chromogenic, or silver), completely replacing IHC or only for tumors with an ambiguous (2+) IHC score (II, B) [59] .…”

Section: Discussionmentioning

confidence: 99%

“…Many studies investigated receptor conversion both in the neoadjuvant setting and at metastatic relapse [ 9 , 11 , 60 , 61 ] . Nevertheless, most of them were small, retrospective, included patients receiving different drug regimens, and applied distinct definitions of HER2-positivity, thus leading to many biases and low statistical power.…”

Section: Discussionmentioning

confidence: 99%

Loss of HER2 in breast cancer: biological mechanisms and technical pitfalls

Morganti¹,

Ivanova²,

Ferraro³

et al. 2022

Cancer Drug Resist

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Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers; however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER2 after neoadjuvant therapy and at metastatic relapse and identified clinicopathological variables more frequently associated with this event. Nevertheless, the biological mechanisms underlying HER2 loss are still poorly understood. HER2 downregulation, intratumoral heterogeneity, clonal selection, and true subtype switch have been suggested as potential causes of HER2 loss, but translational studies specifically investigating the biology behind HER2 loss are virtually absent. On the other side, technical pitfalls may justify HER2 loss in some of these samples. The best treatment strategy for patients with HER2 loss is currently unknown. Considering the prevalence of this phenomenon and its apparent correlation with worse outcomes, we believe that correlative studies specifically addressing HER2 loss are warranted.

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Loss of HER2‐positivity following neoadjuvant targeted therapy for breast cancer is not associated with inferior oncologic outcomes

Cited by 11 publications

References 21 publications

Incidence and prognostic impact of HER2‐positivity loss after dual HER2‐directed neoadjuvant therapy for HER2+ breast cancer

Incidence and prognostic impact of HER2‐positivity loss after dual HER2‐directed neoadjuvant therapy for HER2+ breast cancer

Androgen Receptor: A New Marker to Predict Pathological Complete Response in HER2-Positive Breast Cancer Patients Treated with Trastuzumab Plus Pertuzumab Neoadjuvant Therapy

Loss of HER2 in breast cancer: biological mechanisms and technical pitfalls

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