Exploring the Heterogeneity of HER2 gene status and Expression in Non-Positive Breast Cancer Patients: Insights from Immunohistochemistry and Fluorescence In Situ Hybridization

doi:10.21203/rs.3.rs-5035261/v1

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Exploring the Heterogeneity of HER2 gene status and Expression in Non-Positive Breast Cancer Patients: Insights from Immunohistochemistry and Fluorescence In Situ Hybridization

https://doi.org/10.21203/rs.3.rs-5035261/v1

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Breast cancer became the most prevalent malignancy among women, and HER2 expression status is critical for treatment decisions. With the emergence of ADC drugs, HER2 low-expressing patients who previously did not respond well to traditional anti-HER2 therapies may now benefit. In this study, we evaluated HER2 expression in 349 HER2-non-positive breast cancer patients using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Our analysis revealed that HER2-low tumors exhibited fewer grade III tumors (39.74% and 55.65%, respectively, P = 0.005) and higher positivity for estrogen receptor (ER, 88.89% vs. 61.74%, P < 0.001) and progesterone receptor (PR, 84.62% vs. 57.39%, P < 0.001) compared to HER2-0 tumors. IHC interpretation varied widely, with antibodies showing only 67.3% and 65.3% agreement in HER2-0 and HER2-2 + groups (P < 0.001), respectively. Similarly, pathologists showed limited agreement, with 66.4% and 63.7% consistency in HER2-0 and HER2-2 + groups (P < 0.001). FISH analysis revealed significant differences in HER2 gene signals between HER2-0 and HER2-low tumors, but no clear cut-off value could be identified. Notably, HER2 gene red signal averages were mostly ≥ 2 and < 4, with HER2-0 tumors primarily ≤ 2.5, and HER2/CEP17 ratio mostly between 1 and 2, with HER2-0 tumors primarily ≤ 1.4. Despite distinct clinicopathological features, FISH remains inadequate for distinguishing HER2-low from HER2-0 expression. Future studies are needed to improve HER2 assessment in this challenging subset of patients.

Breast cancer

HER2-low

FISH

Immunohistochemistry staining

In recent years, Breast cancer has become the most commonly diagnosed cancer in women [1]. The hormone receptor (HR) and epidermal growth factor receptor 2 (HER2, or ERBB2) are well-recognized biomarkers for the treatment of breast cancer [2], with HER2 determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Approximately 80%-85% of breast cancers are defined as HER2 negative, while the majority of these tumors still express detectable levels of HER2 protein on cell membranes. This includes two thirds of HR positive and one third of triple-negative tumors with low HER2 expression (HER2 IHC score of 1 + or 2+/ISH not amplified) [3]. Unfortunately, anti-HER2 monoclonal antibodies that target HER2-low expression have failed to demonstrate any clinical benefit [4]. However, several clinical trials have shown promising results with anti-HER2 antibody-drug conjugates (ADCs) in the treatment of HER2-low breast cancer [5–10]. In particular, trastuzumab-deruxtecan (T-Dxd), has recently been approved by the US Food and Drug Administration as the first targeted therapy to treat HER2-low breast cancer [11].

Given the efficacy of ADCs in treating HER2-low breast cancer, more challenges have been identified in the interpretation of HER2 protein expression by immunohistochemistry (IHC) in clinical practice. A study conducted among 18 pathologists at Yale University examined the interpretation of HER2 IHC scores for 170 breast cancer biopsies. The findings suggested that the current standard HER2 IHC assay exhibits poor scoring accuracy in the low range (0 and 1+) [12]. This poor agreement in HER2 IHC scoring can lead to misassignment of ADCs therapy. To address this discordance, several studies have been designed to identify an effective quantitative method for distinguishing HER2-low from HER2-0 [13–15]. Additionally, the DESTINY-Breast06 trial is evaluating T-DXd in patients with HER2-ultra low breast tumors (IHC > 0 to < 1+), providing insights that may improve the identification of patient populations expected to benefit from HER2-targeted antibody-drug conjugates [16]. This trial also suggests that we should investigate the true statuses of HER2 gene in tumors with different HER2 protein expression levels. In this study, we applied FISH to perform a comprehensive stratification of HER2 gene among HER2 negative breast cancer tumors, including HER2-0 and HER2-low. Our aim was to reveal the actual status of HER2 in the large population of HER2 negative breast cancer patients, who account for 80%-85% of all cases.

Study subjects and clinical data

A total of 349 cases of paraffin-embedded samples for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were obtained from female patients with invasive ductal breast carcinoma who had undergone surgeries at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between 2018 and 2019. All of these patients had not received pre-operative chemotherapy or radiotherapy. In the current study, breast cancer patients were categorized as follows based on HER2 status determined by IHC and FISH of archive results: HER2-0 (n = 115), HER2-1+ (n = 104) and HER2-2+ (n = 130), according to the World Health Organization Classification of Tumours of the Breast, 5th edition. The study was approved by the Medical Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology and informed consent was obtained from all patients. The experiments performed in this study adhere to the current laws of China regarding the use of human subjects.

The HER2 status was re-examined using both fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in all cases to further investigate HER2 expression in HER2-0 and HER2-low breast cancer. The interpretations were independently performed by two experienced pathologists.

Fluorescence in situ hybridization

All patients in Group HER2-2 + were formerly confirmed to be HER2 negative using the human HER2 gene amplification test kit (Wuhan HealthCare Biotechnology Co., Ltd) via FISH. To assess HER2 gene expression, the LBP DNA probe Kit (Guangzhou LBP Medicine Science & Technology Co., Ltd.) was utilized to determine the status of all enrolled patients. For each sample, HER2 and CEP17 signals were evaluated in approximately 30 invasive tumor cells to calculate the average HER2 signal and HER2/CEP17 ratio.

Immunohistochemistry

All patients enrolled in this study were initially tested using clone 4B5 and then retested with clone EP3. Here is the detailed information about the antibodies used: clone 4B5 (Ventana, Roche) and clone EP3 (GuangZhou LBP Medicine Science & Technology Co., Ltd.), both of which are rabbit monoclonal antibodies. The results were interpreted according to the 2023 ASCO guidelines [17] as follows: ① HER2-0: no staining or incomplete membrane staining that is faint/ barely perceptible in ≤ 10% of tumor cells; ② HER2-1+: incomplete membrane staining that is faint/ barely perceptible in > 10% of tumor cells; ③ HER2-2+: weak to moderate complete membrane staining observed in > 10% of tumor cells.

Statistical analysis

To assess the clinicopathologic feature differences among HER2-0, HER2-1+, and HER2-2 + groups, as well as between HER2-0 and HER2-low groups, the χ2 test or two-sided Fisher's exact test were utilized. To assess the concordance of HER2 expression interpretation by IHC between two different HER2 clones and between two pathologists, the paired t-test was employed. The χ2 test was used to estimate the differences in HER2 gene distribution between HER2-0, HER2-1+, and HER2-2 + groups. Finally, one-way analysis of variance was utilized to measure the differences in FISH results among the HER2-0, HER2-1+, and HER2-2 + groups.

Clinicopathologic characteristics of the HER2-low and HER-0 breast cancer cohort

In this study, we enrolled 349 HER2-negative breast cancer patients, including 115 patients in the HER2-0 group, 104 patients in the HER2-1 + group, and 130 patients in the HER2-2 + group. These patients were generally reclassified into two groups: HER2-0 (HER2-0, n = 115) and HER2-low (HER2-1 + and HER2-2+, n = 234). The classification used in this study is based on the HER2 IHC score obtained through clone 4B5. For baseline clinicopathologic characteristics, we found that HER2-low had fewer grade III tumors than HER2-0 (39.74% and 55.65%, respectively, P = 0.005, χ2 test). ER (88.89% and 61.74%, respectively, P < 0.001, χ2 test) and PR (84.62% and 57.39%, respectively, P < 0.001, χ2 test) positivity was more common in HER2-low tumors than HER2-0. When stratified by HER2 expression by IHC, a similar situation was found between HER2-0, HER2-1 + and IHC-2 in histologic grade, ER and PR expression (P < 0.05, χ2 test) (Table 1).

Table 1

Baseline clinicopathologic characteristics of HER2 HER2-0, HER2-1 + and HER2-2+/FISH- breast cancer cohort.
	HER2-0 (n = 115)	HER2-low (n = 234)	P*	HER2-0 (n = 115)	HER2-1+ (n = 104)	HER2-2+/FISH- (n = 130)	P*
Age (years)
< 50	54	114	0.757	54	60	54	0.047
≥ 50	61	120		61	44	76
Grade
I-II	51	141	0.005	51	57	84	0.006
III	64	93		64	47	46
pT
pT1	65	123	0.889	65	56	67	0.440
pT2	48	103		48	41	62
pT3	2	5		2	4	1
NA	0	3		0	3	0
pN
pN0	56	124	0.389	56	56	68	0.656
pN1	32	66		32	28	38
pN2	19	24		19	10	14
pN3	7	18		7	10	8
NA	1	2		1	0	2
Ki67 percentage
< 20	40	73	0.501	40	32	41	0.791
≥ 20	75	161		75	72	89
ER
Negative	44	26	0.000	44	14	12	0.000
Positive	71	208		71	90	118
PR
Negative	49	36	0.000	49	17	19	0.000
Positive	66	198		66	87	111
* χ2 test or two-sided Fisher’s exact test.
Values that are not available (NA) were excluded from P-value calculation.

Table 2

Baseline clinicopathologic characteristics of HER2 HER2-0, HER2-1 + and HER2-2+/FISH- in HR negative breast cancer cohort.
	HER2-0 (n = 42)	HER2-low (n = 25)	P*	HER2-0 (n = 42)	HER2-1+ (n = 14)	HER2-2+/FISH- (n = 11)	P*
Age (years)
< 50	19	11	0.921	19	7	4	0.831
≥ 50	23	14		23	7	7
Grade
I-II	3	3	0.664	3	1	2	0.397
III	39	22		39	13	9
pT
pT1	22	4	0.004	22	1	3	0.005
pT2	20	20		20	12	8
pT3	0	1		0	1	0
pN
pN0	22	18	0.342	22	12	6	0.393
pN1	10	2		10	0	2
pN2	5	2		5	1	1
pN3	4	2		4	1	1
NA	1	1		1	0	1
Ki67 percentage
< 20	1	1	1.000	1	0	1	0.345
≥ 20	41	24		41	14	10
* χ2 test or two-sided Fisher’s exact test.
Values that are not available (NA) were excluded from P-value calculation.

Dai et al. delved into the distinctive nature of HER2-low breast cancer across various hormone receptor statuses [18]. We, in turn, examined the nuances between HER2-0 and HER2-low in different hormone receptor contexts. According to the baseline clinicopathologic features observed in HR negative breast cancer, larger tumor size was more common in HER2-low than HER2-0 (P = 0.004, two-sided Fisher’s exact test), and in HER2-1 + than HER2-0 (85.71% and 47.62%, respectively, P = 0.005, two-sided Fisher’s exact test) (Tabel 2). In HR positive breast cancer, Ki67 percentage was higher in HER2-low than HER2-0 (P = 0.004, χ2 test) and in HER2-2 + and HER2-0 (P = 0.016, χ2 test) (Table 3).

Table 3

Baseline clinicopathologic characteristics of HER2 HER2-0, HER2-1 + and HER2-2+/FISH- in HR positive breast cancer cohort.
	HER2-0 (n = 73)	HER2-low (n = 209)	P*	HER2-0 (n = 73)	HER2-1+ (n = 90)	HER2-2+/FISH- (n = 119)	P*
Age (years)
< 50	35	103	0.892	35	53	50	0.053
≥ 50	38	106		38	37	69
Grade
I-II	48	138	0.966	48	56	82	0.600
III	25	71		25	34	37
pT
pT1	43	114	0.664	43	51	63	0.497
pT2	28	88		28	33	55
pT3	2	4		2	3	1
NA	0	3		0	3	0
pN
pN0	34	106	0.250	34	44	62	0.498
pN1	22	64		22	28	36
pN2	14	22		14	9	13
pN3	3	16		3	9	7
NA	0	1		0	0	1
Ki67 percentage
< 20	39	72	0.004	39	32	40	0.016
≥ 20	34	137		34	58	79
* χ2 test or two-sided Fisher’s exact test.
Values that are not available (NA) were excluded from P-value calculation.

IHC is not a consistent method to distinguish HER2-low from HER2-0

We conducted a comparative analysis of HER2 expression results obtained using clone 4B5 and EP3, revealing significant inconsistencies in the HER2-0 (P < 0.001) and HER2-2+ (P < 0.001) groups. The concordance rates for HER2-0 and HER2-2 + were 67.3% and 65.3%, respectively. Additionally, we enlisted the assistance of two highly experienced pathologists to evaluate HER2 expression using clone EP3. Again, inconsistencies were observed in the HER2-0 (P < 0.001) and HER2-2+ (P < 0.001) groups, with concordance rates of 66.4% and 63.7%, respectively.

Distinctness of distribution of HER2/CEP17 ratio and average HER2 signals in different HER2 protein expression groups of breast cancer

We divided these patients into three groups: HER2-0, HER2-1+, and HER2-2 + based on the HER2 IHC values obtained using clone 4B5. To determine the HER2 amplification status within each group, we employed FISH analysis. According to the 2023 ASCO guidelines¹⁷, HER2 amplification was observed in 0.9% (1/105) of patients in the HER2-0 group, 2.88% (3/104) in the HER2-1 + group, and 1.54% (2/130) in the HER2-2 + group. The majority of patients in each group exhibited a HER2/CEP17 ratio between 1 and 2. Notably, more patients in the HER2-2 + group had a HER2/CEP17 ratio ranging from 1 to 2 compared to the HER2-1 + group among all patients (95.38% vs 85.58%, P = 0.036, two-sided Fisher’s exact test) (Fig. 1a) and hormone receptor (HR)-positive patients (95.80% vs 86.67%, P = 0.045, two-sided Fisher’s exact test) (Fig. 1e). No statistically significant differences were observed among HR-negative patients across the HER2-0, HER2-1+, and HER2-2 + groups (P > 0.05, two-sided Fisher’s exact test) (Fig. 1c).

More precisely, the HER2/CEP17 ratio was primarily limited to 1.3 or less, with frequencies of 94.34%, 85.39%, and 83.87% observed in the HER2-0, HER2-1+, and HER2-2 + groups, respectively. Significant differences in HER2/CEP17 ratio were observed between the HER2-0 and HER2-1 + groups (P = 0.036) as well as between the HER2-0 and HER2-2 + groups (P = 0.012). Furthermore, a higher proportion of patients in the HER2-0 group demonstrated HER2/CEP17 ratio not exceeding 1.3 compared to the HER2-low group (94.34% vs. 84.51%, P = 0.012).

The majority of patients in each group exhibited average HER2 signals between 1 and 4. Notably, more patients in the HER2-2 + group had average HER2 signals, ≥ 2 and < 4, compared to the HER2-0 group among all patients (66.15% vs 60.53%, P = 0.022, two-sided Fisher’s exact test) (Fig. 1b). No statistically significant differences were found among HR-negative or -positive patients across HER2-0, HER2-1 + and HER2-2 + groups (P > 0.05, two-sided Fisher’s exact test) (Fig. 1d and f).

Specifically, the average HER2 signals did not exceed 2.5 in the majority of cases, with frequencies of 80.87%, 69.00%, and 69.84% in the HER2-0, HER2-1+, and HER2-2 + groups, respectively. It showed significant difference between the HER2-0 and HER2-1 + groups (P = 0.044) as well as between the HER2-0 and HER2-2 + groups (P = 0.048). Furthermore, a higher proportion of patients in the HER2-0 group exhibited average HER2 signals not exceeding 2.5 compared to the HER2-low group (80.87% vs. 69.47%, P = 0.024).

Distinct Expression Profiles of HER2 Gene in Breast Cancer with Different HER2 Protein Expression Patterns

Based on the classification of HER2 expression by clone 4B5, HER2/CEP17 ratio was found to be significantly higher in the HER2-low group compared to the HER2-0 group, while the opposite trend was observed for average HER2 signals. However, these differences were not statistically significant (P = 0.116 and P = 0.055, respectively) (Fig. 2a and c). When considering the distribution of HER2/CEP17 ratio and average HER2 signals across the HER2-0, HER2-1+, and HER2-2 + groups, we observed that the values for both HER2/CEP17 ratio and average HER2 signals primarily fell within the ranges of (1,2) and [2,4), respectively. To enhance the distinguishability between different values, we opted to re-analyze the data using log2 transformation.

After applying log2 transformation, the HER2/CEP17 ratio was found to be significantly higher in the HER2-low group compared to the HER2-0 group (P = 0.026) (Fig. 2b). Conversely, the average HER2 signals showed a significant decrease in the HER2-low group compared to the HER2-0 group (P = 0.001) (Fig. 2d). We also analyzed the HER2/CEP17 ratio and average HER2 signals based on HER2 expression determined by immunohistochemistry (IHC). The HER2/CEP17 ratio was found to be higher in the HER2-2 + group compared to the HER2-0 group (P = 0.039) (Fig. 3a). Similarly, the average HER2 signals were higher in the HER2-2 + group compared to the HER2-0 group (P = 0.005) (Fig. 3c). After applying log2 transformation, a similar difference was observed between the HER2-2 + and HER2-0 groups in terms of HER2/CEP17 ratio (P = 0.021) (Fig. 3b) and average HER2 signals (P = 0.003) (Fig. 3d). Furthermore, average HER2 signals were also observed to be higher in the HER2-1 + group compared to the HER2-0 group (P = 0.012) (Fig. 3d).

Although significant differences were observed in HER2/CEP17 ratio and average HER2 signals between the HER2-0 and HER2-low groups, no effective cutoff values could be determined. The square of the ROC for HER2/CEP17 ratio and average HER2 signals was 0.528 and 0.595, respectively, indicating that FISH is not an effective tool for distinguishing between HER2-0 and HER2-low.

Then, the groups were reclassified based on HER2 IHC score using clone EP3. Only a significant difference was found between the HER2-0 and HER2-2 + groups in average HER2 signals after log2 transformation (P = 0.013).

Human epidermal growth factor receptor 2 (HER2) is a well recognized prognostic and therapeutic biomarker in breast cancer and it was defined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). These patients of breast cancer with HER2 positive can be benefit from anti-HER2 therapy, which is only account for 15%-20% of breast cancer. In standard care for breast cancer patients, HER2-0, HER2-1 + and HER2-2+/FISH- are all classified as HER2 negative and no clinical significance in distinguishing between these categories because of no clinical benefits in patients of breast cancer in the first generation of HER2-targeted therapies.

However, recent data on the efficacy of new antibody-drug conjugate (ADC) therapies in patients with BC with low HER2 protein expression opens the door to a new population of HER2-low breast cancer, indicating a new era of HER2 classification. In the current study, we found a significance between HER2-0 and HER2-low in histological grade and expression of estrogen receptor (ER), progesterone receptor (PR) and Ki67. In the cohort of Lei-Jie Dai et al, no significant difference between HER2-0 and HER2-low in clinicopathological characteristics was identified, while there is significant difference in RNA and protein level and the prognosis between HER2-0 and HER2-low [18].

In consideration of the efficacy of ADC therapies in patients with HER2-low breast cancer and the significant difference between it from HER2-0 and HER2-positive, how to distinguish HER2-low from HER2-0 seems of great importance. In clinical practice, the status of HER2 is defined by IHC and FISH, while the clone of HER2 antibody, different pathologists and different laboratory are all can have an impact on the interpretation of the result of IHC of HER2 [19, 20]. In general, the accordance is low. In this study, EP3 was used to compare with the archive original medical records of HER2 which was tested by 4B5. A significant difference was found between HER2-0 groups and HER2-(2+/FISH-) groups, and even between the interpretation of IHC HER2 of different pathologists by the same clone EP3. Recently, some researches designed an AI to improve this situation and it seems to give us a good result [21]. However, it is worth noting that a potential limitation exists in the study. The definitions of the HER2-0 and HER2-low groups were predetermined, potentially introducing a degree of bias in their designation. Consequently, these findings highlight the limitations of IHC in accurately distinguishing between HER2-low and HER2-0 cases.

To further confirm the expression of HER2 at the gene level in these “HER2 non-positive” cases, FISH analysis was employed. We compared the FISH results obtained by two pathologists in patients who exhibited average HER2 signals of no less than 3 and found no significant difference between them. Based on these findings, it appears that FISH, as a semiquantitative method, exhibits better consistency compared to IHC. However, this does not necessarily imply that FISH is an optimal method for distinguishing HER2-low from HER2-0 cases. Additionally, when comparing the HER2/CEP17 ratio and the average HER2 signals between HER2-0 and HER2-low groups, both analyses revealed significant differences. Furthermore, we established cut-off values for both HER2/CEP17 ratio and HER2 average signals, but neither exhibited satisfactory sensitivity and specificity. A critical stratification analysis of HER2/CEP17 ratio revealed that the majority of cases had HER2/CEP17 ratio concentrated between 1 and 2 (92.17%) and not exceeding 1.3 (94.34%). Notably, both of these ranges were more prevalent in HER2-0 cases compared to HER2-low cases. Similarly, the analysis of HER2 average signals yielded a similar observation, with a higher frequency of cases with signals not exceeding 2.5 in HER2-0 compared to HER2-low.

These findings suggest that while FISH can reveal population-level differences between HER2-0 and HER2-low cases, it remains challenging to make such distinctions in individual patients. Therefore, the accurate definition of HER2-0 and HER2-low remains a critical issue in practical pathology.

Multiple potential methods have been developed to assess the status of HER2, including the reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) assay. However, a study conducted by Shu L and colleagues compared HER2 mRNA levels between HER2 0 and 1 + tumors, revealing that both exhibited significantly lower levels compared to IHC 2+/FISH − tumors. Notably, neither IHC nor qRT-PCR appears to be an optimal tool for accurately quantifying HER2-low expression, particularly in HER2 1 + patients [22].

In "HER2 non-positive" cases, the expression of the HER2 gene tended to be closer to normal in a larger proportion of the HER2-0 group. Nevertheless, FISH remains a viable tool for identifying the relative and specific gene expression levels, which raises the question of what threshold of HER2 gene expression would render a patient eligible for ADC therapy. ADCs are comprised of four crucial components: the target antigen, the antibody construct, a payload (most frequently a cytotoxic agent), and a linker moiety that bridges the payload and the antibody [23]. Notably, the pharmacological mechanism of ADCs does not solely rely on high HER2 expression. Instead, its primary mode of action is attributed to its bystander benefit and high loading ratio [24]. The DESTINY-Breast 04 study revealed that regardless of the HR status, T-Dxd therapy in HER2-low cases significantly enhances progression-free survival (PFS) and overall survival (OS) when compared to chemotherapy. Specifically, the risk of disease progression and death decreased by 50% and 36%, respectively [5]. Furthermore, certain studies have hinted at the promising potential of novel ADCs in improving PFS and OS in patients with HR+/HER2- metastatic breast cancer. However, it is worth noting that these studies also highlighted some limitations, including a small sample size, limited diversity in the patient population, and the need for further verification of long-term efficacy and safety [24–26].

In conclusion, IHC and FISH may not be reliable methods for distinguishing HER2-low from HER2-0 status. Instead, FISH, being a relatively consistent technique, can be employed to assess the HER2 gene expression status, providing valuable insights for ADC therapy decisions. In the future, it is imperative to delve deeper into the HER2 gene expression patterns in breast cancer patients with low HER2 expression who are likely to respond favorably to ADC drug therapy. This will enable us to identify these patients with greater precision and efficacy, thereby guiding the treatment strategies for other similar patients.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This research was supported by Jingjian Pathology·Daiichi Sankyo Breast Cancer Research Fund Project (No. JJlXA2022-012).

Author Contributions

Jingmin Zhong: Data curation, funding acquisition, writing-original draft and editing.

Beibei Gao: Data curation, formal analysis, writing-review.

Qingjie Wang: Data curation.

Jun He: Methodology.

Danjv Luo: Methodology.

Cheng Zhang: Methodology.

Jun Fan: Writing-review.

Xiu Nie: Supervision, writing-review.

Data Availability Statement

Data sharing not applicable to this article.

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No competing interests reported.

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Exploring the Heterogeneity of HER2 gene status and Expression in Non-Positive Breast Cancer Patients: Insights from Immunohistochemistry and Fluorescence In Situ Hybridization

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Version 1

Abstract

Figures

Introduction

Materials and methods

Study subjects and clinical data

Fluorescence in situ hybridization

Immunohistochemistry

Statistical analysis

Results

Clinicopathologic characteristics of the HER2-low and HER-0 breast cancer cohort

IHC is not a consistent method to distinguish HER2-low from HER2-0

Distinct Expression Profiles of HER2 Gene in Breast Cancer with Different HER2 Protein Expression Patterns

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1