Receptor discordance after neoadjuvant chemotherapy and its impact on disease-free survival.

Tural, Deniz; Karaca, Mustafa; Hacioglu, Bekir; Bilgetekin, İrem; Bi̇lgi̇n, Burak; Koçoğlu, Hakan; Özet, Gülsüm; Erdoğan, Bülent; Şendur, Mehmet Ali Nahit; Aytekin, Aydın; Benekli, Mustafa; Özet, Ahmet

doi:10.1200/jco.2016.34.15_suppl.e12518

Cited by 10 publications

(21 citation statements)

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“…Prior studies have reported HER2-discordance ranging from 13% to 24% in those with residual disease. 16,17 However, many of these investigations were not solely focused on the HER2-positive population, and the proportion of patients with HER2-positive disease was low, in contrast to the present study. 4,15 In addition to the large size, focus, and nearly 4 years of median oncologic follow up of the present study, the vast majority of patients also received adjuvant targeted therapy per the standard of care.…”

Section: Discussioncontrasting

confidence: 69%

“…The estimated 3‐year OS for patients with HER2‐negative disease is 50% in their cohort, which is concerning for its significant divergence from contemporary outcomes in this population. Finally, Tural and colleagues reported that HER2‐discordance was independently associated with inferior RFS from a cohort of 138 HER2‐positive patients 16 . The low pCR rate of 18%, low median follow‐up of 35 months, poor prognosis of patients with residual disease, and lack of adjustment for RCB class call into question the generalizability of that finding, however.…”

Section: Discussionmentioning

confidence: 99%

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

Wetzel

Sutton

Gardiner

et al. 2021

Journal of Surgical Oncology

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Background Patients with human epidermal growth factor receptor 2 (HER2)‐positive breast cancer are treated with trastuzumab‐based neoadjuvant therapy (NAT); some patients with residual disease post‐NAT show loss of HER2 amplification and has been inconsistently associated with oncologic outcomes. Methods We queried our multi‐institutional cancer registry for women with HER2‐positive breast cancer undergoing NAT from 2011 to 2018. Clinicopathologic, treatment‐related, and outcomes data were collected. Kaplan–Meier and Cox proportional hazards analysis were used to evaluate oncologic outcomes. Results A total of 348 patients were identified; 166 (48%) had a pathologic complete response. Of the 182 patients with residual disease, 87 (48%) were HER2‐positive, 34 (19%) were HER2‐negative, and 61 (33%) were HER2‐unknown, with a median follow‐up of 44 months. There were no factors associated with HER2 loss apart from age. On Kaplan–Meier analysis, estimated 5‐year recurrence‐free survival (RFS) and overall survival (OS) for patients with HER2‐positive residual disease was 81% and 92%, respectively, and 74% (log rank p = 0.75) and 81% (p = 0.35) in patients with HER2‐negative residual disease. Conclusion The loss of HER2‐positivity following NAT is not associated with worse 5‐year RFS or OS. We do not recommend retesting HER2 status following NAT for the purpose of clinical management; these patients should complete targeted adjuvant therapy.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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

Wetzel

Sutton

Gardiner

et al. 2021

Journal of Surgical Oncology

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“…We found a statistically significant decrease in PR expression values between biopsy and surgical specimens after NAT, which is consistent with other reports where the PR, along with the Ki67 index, are the most commonly altered biomarkers after NAT administration [7,15,16,31]. Contrary to what has been reported for Ki67, PR expression loss has been associated with worse tumor characteristics [15] and poor clinical outcomes [23,32,40]. It has also been shown that loss of PR expression may be an indicator of a decrease of hormone sensitivity in tumor cells, activation of alternate proliferation pathways such as PI3K/AKT/mTOR [41,42], and also, the induction of a non-functional ER state which could lead to a diminished response to endocrine therapy, specifically in ERpositive/PR-negative tumors [18,43].…”

Section: Discussionsupporting

confidence: 90%

“…Nevertheless, many retrospective studies have reported changes in biomarker expression in surgical specimens after NAT administration [15][16][17][18][19][20][21]. The main changes correspond to discordances in hormone receptors and HER2 status [22], along with decreases in the percentage of expression, especially for PR and Ki67 [23][24][25][26]. Most of these studies end up suggesting the need to re-evaluate its expression, justifying its importance not only to assess tumor response to treatment but to adjust therapy according to these changes [3,27].…”

Section: Introductionmentioning

confidence: 99%

Effect of neoadjuvant therapy on breast cancer biomarker profile

et al. 2020

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Background: Breast cancer clinical management requires the assessment of hormone receptors (estrogen (ER) and progesterone receptor (PR)), human epidermal growth factor receptor 2 (HER2) and cellular proliferation index Ki67, by immunohistochemistry (IHC), in order to choose and guide therapy according to tumor biology. Many studies have reported contradictory results regarding changes in the biomarker profile after neoadjuvant therapy (NAT). Given its clinical implications for the disease management, we aimed to analyze changes in ER, PR, HER2, and Ki67 expression in paired core-needle biopsies and surgical samples in breast cancer patients that had either been treated or not with NAT. Methods: We included 139 patients with confirmed diagnosis of invasive ductal breast carcinoma from the Colombian National Cancer Institute. Variation in biomarker profile were assessed according to NAT administration (NAT and no-NAT treated cases) and NAT scheme (hormonal, cytotoxic, cytotoxic + trastuzumab, combined). Chisquared and Wilcoxon signed-rank test were used to identify changes in biomarker status and percentage expression, respectively, in the corresponding groups. Results: We did not find any significant variations in biomarker status or expression values in the no-NAT group. In cases previously treated with NAT, we did find a statistically significant decrease in Ki67 (p < 0.001) and PR (p = 0.02605) expression. When changes were evaluated according to NAT scheme, we found a significant decrease in both Ki67 status (p = 0.02977) and its expression values (p < 0.001) in cases that received the cytotoxic treatment. Conclusions: Our results suggest that PR and Ki67 expression can be altered by NAT administration, whereas cases not previously treated with NAT do not present IHC biomarker profile variations. The re-evaluation of these two biomarkers after NAT could provide valuable information regarding treatment response and prognosis for breast cancer patients.

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“…For patients with locally advanced breast cancer, HER2 overexpression is an independent risk factor regarding 5-year disease-free survival (DFS). In the multivariate analysis by Tural et al [ 12 ], clinical stage of the tumor, transformation of HER2 from positive to negative and triple negative receptor status significantly influenced DFS. Li et al [ 13 ] included 2847 patients from eight studies and found that patients with hormone receptors (HR) which changed from positive to negative had worse DFS.…”

Section: Discussionmentioning

confidence: 99%

HER2 changes to positive after neoadjuvant chemotherapy in breast cancer: A case report and literature review

Luo¹,

Jiang²,

He³

et al. 2022

WJCC

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BACKGROUND As the most common cancer in women, breast cancer is the leading cause of death. Most patients are initially diagnosed as stage I-III. Among those without distant metastases, 64% are local tumors and 27% are regional tumors. Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy (NACT). It is worth noting that the status of tumor cell biomarkers is not consistently static. Endocrine-related estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa , especially in luminal B subtype after NACT. In addition, determination of HER2 status currently mainly relies on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), but FISH is commonly used when the result of IHC is uncertain. HER2 is regarded as negative when the IHC result is 0/1+ without the addition of FISH. To the best of our knowledge, this is the first report of a case harboring HER2 status transformation and IHC1+ with positive amplification by FISH after NACT. CASE SUMMARY A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup. Biopsies of the right breast lesion and axillary lymph nodes were obtained. The results pointed to invasive ductal carcinoma with the IHC result for ER (80%), PR (60%), Ki-67 (20%) and ambiguous expression of HER2 (IHC 2+) with negative amplification by FISH (HER2/CEP17 ratio of 1.13). She underwent surgery after NACT. The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm × 0.8 cm × 0.5 cm and had spread to one of fifteen dissected lymph nodes. Retesting of the specimen showed that the tumor was positive for ER (2+, 85%) and PR (2+, 10%) but negative for HER2 by IHC (1+). Also Ki-67 had dropped to 2%. The patient was regularly monitored every 3 mo without evidence of recurrence. CONCLUSION Biomarker status should be reassessed after NACT especially in luminal subtypes.

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Receptor discordance after neoadjuvant chemotherapy and its impact on disease-free survival.

Cited by 10 publications

References 0 publications

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

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

Effect of neoadjuvant therapy on breast cancer biomarker profile

HER2 changes to positive after neoadjuvant chemotherapy in breast cancer: A case report and literature review

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