Lowering the Bar – to Treatment

Exploring the impact of the HER2-low biomarker in breast cancer stratification

08/25/2023 | 8 min read

sponsored by Daiichi Sankyo, Inc. & AstraZeneca

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic:

HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

Please see Important Safety Information below.

Shabnam Jaffer is Chair of the Department of Pathology and Laboratory Medicine at Lenox Hill Hospital, Northwell Health, New York. She is also Professor of Pathology at the Hofstra Zucker School of Medicine. Jaffer has been practicing breast pathology for over 20 years.

Paolo Tarantino is a Breast Medical Oncologist and Advanced Research Fellow at Dana Farber Cancer Institute and Harvard Medical School. His research focuses on HER2-positive and HER2-low breast cancer, and the development of antibody drug conjugates.

Tarantino: Back in the 1990s, we recognized that certain breast tumors – about 15 percent – harbored amplification of the HER2 oncogene that leads to overexpression of the HER2 protein on the cell membrane – an oncogenic event that makes tumor cells more aggressive (1-3). We also learned that we could improve outcomes for patients with HER2-positive breast cancers by blocking the HER2 signal with a monoclonal antibody (3, 4). In 1998, the first targeted therapy for HER2-positive breast cancer was approved by the United States Food and Drug Administration (FDA), and was subsequently approved for early-stage breast cancer, and ultimately followed by many other HER2-directed agents (3, 4). To be clear, these agents were only approved for the treatment of HER2-positive breast cancer as defined by immunohistochemistry (IHC) testing – and not for the 85 percent of breast tumors defined as HER2-negative (1, 3).

However, this binary definition of positive and negative has been challenged by potent antibody drug conjugates (ADCs) that can exploit lower expression of HER2 on the cell membrane to selectively deliver potent chemotherapies (1). The first ADC to be approved for eligible patients with tumors that express lower levels of HER2 protein is fam-trastuzumab deruxtecan-nxki (5). Indeed, this advance has led to a three-tiered approach to HER2 classification: HER2-positive, HER2-low, and HER2-0* – some tumors for which HER2 cannot be detected by IHC (6).

Jaffer: For a pathologist working in 2023, HER2-low is extremely relevant. Indeed, Dr. Tarantino and I both just attended the USCAP 2023 meeting in New Orleans, where the two most popular topics in breast pathology were HER2-low and artificial intelligence (AI) – with some of the AI material actually focused on HER2-low interpretation.

The positive results of the DESTINY-Breast04 trial, in particular, have highlighted the crucial role of the pathologist in identifying HER2-low patients for the treating oncologist (6). Pathologists are not only aware of HER2-low, but they are hungry to know more – particularly, how to effectively recognize and report HER2-low status.

In many ways, the pathologist and the oncologist are joined at the hip – if a subject, like HER2-low, becomes clinically relevant to the oncologist, it will always become clinically relevant to the pathologist.

Tarantino: We’ve seen a major evolution in the way we treat patients with HER2-low metastatic breast cancer. In the past, we did not really differentiate in treatment algorithms between HER2-low and HER2 IHC 0 – they were both included in the macro category of HER2-negative and treated only according to expression of hormone receptors (HR) (7). Consequently, we would treat HR-positive/HER2-negative tumors in one way and triple-negative tumors in another. Today, these two categories are further subdivided into HER2-low and HER2 IHC 0 (1, 8). As shown in the aforementioned DESTINY-Breast04 trial, ENHERTU significantly improved both progression free survival and overall survival compared with traditional chemotherapy in the overall study population, which included both HR-positive and HR-negative tumors that were demonstrated to be HER2-low using IHC and reflex in situ hybridization (ISH)(7).

Importantly, we know that HER2-low tumors are very frequent – representing around 60 percent of all HR-positive tumors and about 40 percent of all triple-negative tumors (10, 11). In short, we have a wide group of patients who may benefit from an additional treatment option that may improve overall survival (1, 5, 7).

In the DESTINY-Breast04 trial, the most common (≥20 percent) adverse reactions, including laboratory abnormalities, were nausea (76 percent), decreased white blood cell count (70 percent), decreased hemoglobin (64 percent), decreased neutrophil count (64 percent), decreased lymphocyte count (55 percent), fatigue (54 percent), decreased platelet count (44 percent), alopecia (40 percent), vomiting (40 percent), increased aspartate aminotransferase (38 percent), increased alanine aminotransferase (36 percent), constipation (34 percent), increased blood alkaline phosphatase (34 percent), decreased appetite (32 percent), musculoskeletal pain (32 percent), diarrhea (27 percent), and hypokalemia (25 percent).

Enhertu has serious Warnings & Precautions. Please see Important Safety Information, including Boxed WARNINGS, below.

Jaffer: HER2-low has already impacted pathology practice! Oncologists are eager to identify HER2-low in patients with previously treated metastatic breast cancer, so pathologists are suddenly even more sensitive to any variables that can affect detection and interpretation of HER2 including tissue fixation, the antibody clone being used, antigen retrieval protocols, and so on.

The 2018 ASCO-CAP guidelines, which have been recently reaffirmed and updated, present well defined qualitative and quantitative criteria, which help the pathologist choose the appropriate IHC score of 0, 1+, 2+, or 3+ (8). It’s this latter score of 3+ which is considered HER2-positive (8). HER2-positive includes IHC 3+ and 2+ ISH positive, which indicates that a patient may be eligible for HER2-directed therapy. Accordingly, IHC 2+ undergo reflex ISH testing (8).

Before discussions on HER2-low, there was little incentive for pathologists to distinguish between the values of IHC 0 and 1+, which became grouped together with IHC 2+ ISH negative (8). The DESTINY-Breast04 trial brought new appreciation and recognition of HER2-low, which was defined in that study as IHC 1+ or 2+ with a negative ISH result (7). Suddenly, pathologists needed to pay more attention to qualitative and quantitative criteria – especially when distinguishing between IHC 0 and 1+. Indeed, our practices may need to evolve further as newer categories of HER2 expression are explored (10).

Despite objective criteria, interpretation of HER2 expression can be inconsistent; after all, the IHC test is semi-quantitative and observer dependent, making it susceptible to human error (12). Indeed, several studies have demonstrated high interobserver variability – particularly in the low range (12, 13). Some abstracts at USCAP 2023 showed how, with proper education and consensus between breast pathologists, the interobserver variability improves – but it never disappears (14). With borderline cases, where determination of the cutoff value of 10 percent become problematic, pathologists should confer to reach a consensus (15).

Tarantino: I feel that the FDA approval is very clear and helpful. Right now, as well as being approved for eligible patients with previously treated HER2-positive metastatic breast cancer, ENHERTU is approved for treating patients with metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer that have been previously treated with at least one line of chemotherapy in the metastatic setting or have experienced recurrence during or within six months from completing adjuvant chemotherapy (5).

As I mentioned, this treatment may be potentially relevant for more than half of all patients with metastatic breast cancer – so that’s a major population level impact (1). And, again, this drug improved progression free survival and overall survival in DESTINY-Breast04 (7).

Jaffer: The DESTINY-Breast04 trial results and subsequent approval and endorsement of T-DXd by the FDA and the National Comprehensive Cancer Network®(NCCN®) – certainly led to increased communication between pathologists and oncologists about identifying patients with HER2-low tumors. Since August 2022, I noticed there was a great deal of crosstalk that developed between pathologists and oncologists via phone calls, emails, and tumor boards – there has been a real buzz around the topic.

In this era of HER2-low breast cancer, pathologists and oncologists must collaborate to streamline requests and IHC reports – while educating each other. The CAP Breast Biomarker and Breast Invasive Resection report protocols were recently updated (March 2023) to include a note for HER2-low expression (9). We need to use all possible communication channels – national meetings, society meetings, publications, podcasts, social media, and so on – to optimize education and communication between pathologists and oncologists on this topic. In fact, we witnessed the importance of such active efforts at the USCAP 2023 meeting. Tarantino appeared as a guest speaker, further enlightening pathologists on the clinical relevance and importance of HER2-low. No doubt the conversation around HER2-low will continue to evolve with new drugs, trial results, testing advances, and a better understanding of HER2-low tumors. Working together, pathologists and oncologists can more accurately stratify patients and ensure they receive the most appropriate therapy.

*The 2018 ASCO/CAP guidelines classify HER2 status in breast cancer as positive or negative.

Abbreviations: ASCO, American Society of Clinical Oncology; CAP, College of American Pathologists; HER2, human epidermal growth factor receptor 2; USCAP, United States and Canadian Academy of Pathology.

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic:

HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

None.

Interstitial Lung Disease / Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. Median time to first onset was 6 months (range: 0.9 to 32).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109 /L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109 /L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109 /L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level.

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Sixteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 0.9% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.9% of patients, of which 0.4% were Grade 3.

Embryo-Fetal Toxicity

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.

Thrombocytopenia

For Grade 3 thrombocytopenia (platelets <50 to 25 x 109 /L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109 /L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level.

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 1388 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast03, DESTINYBreast02, DESTINY-Breast04, and another clinical trial. Among these patients, 68% were exposed for >6 months and 42% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (75%), decreased white blood cell count (71%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (57%), fatigue (56%), decreased platelet count (48%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (43%), vomiting (42%), increased blood alkaline phosphatase (39%), alopecia (39%), constipation (35%), decreased appetite (32%), hypokalemia (30%), diarrhea (28%), and musculoskeletal pain (26%).

HER2-Positive Metastatic Breast Cancer
^{DESTINY-Breast03}

The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg intravenously every three weeks in DESTINYBreast03. The median duration of treatment was 14 months (range: 0.7 to 30).

Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each).

ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), hypokalemia (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).

HER2-Low Metastatic Breast Cancer
^{DESTINY-Breast04}

The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously every 3 weeks in DESTINYBreast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and hypokalemia (25%).

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 1287 patients with breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.8% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (59%) as compared to younger patients (49%).
Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see complete Important Safety Information and complete Prescribing Information, including Boxed WARNINGS and Medication Guide.

This resource is intended for US healthcare professionals only. Interviewees were compensated for their time.

ENHERTU^®is a registered trademark of Daiichi Sankyo Company, Limited.
©2024 Daiichi Sankyo, Inc. and AstraZeneca. PP-US-ENB-3237 03/24

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Subspecialties Oncology

P Tarantino et al., “HER2-Low Breast Cancer: Pathological and Clinical Landscape,” J Clin Oncol, 38, 1951 (2020). PMID: 32330069.
DJ Slamon et al., “Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene,” Science, 235, 177 (1987). PMID: 3798106.
S Shah & B Chen et al., “Testing for HER2 in Breast Cancer: A Continuing Evolution,” Patholog Res Int, 2011, 903202 (2010). PMID: 21188214.
DY Oh & YJ Bang. “HER2-targeted therapies - a role beyond breast cancer,” Nat Rev Clin Oncol, 1, 33 (2020). PMID: 31548601.
ENHERTU. Prescribing Information. Daiichi Sankyo, Inc.; 2022.
P Tarantino, “ESMO Expert Consensus Statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer,” [Preprint] (2023). PMID: 37269905.
S Modi et al, “Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer,” N Engl J Med, 387, 9 (2022). PMID: 35665782.
AC Wolff et al., “Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update,” Arch Pathol Lab Med, 142, 1364 (2018). PMID: 29846104.
College of American Pathologists (2023). Available at https://bit.ly/43MZudT.
P Tarantino et al., “Navigating the HER2-Low Paradigm in Breast Oncology: New Standards, Future Horizon,” Cancer Discov, 12, 2026 (2022). PMID: 35856622.
P Tarantino et al., “Prognostic and Biologic Significance of ERBB2-Low Expression in Early- Stage Breast Cancer,” JAMA Oncol, 8, 1177 (2022). PMID: 35737367.
H Zhang H et al., “HER2-low breast cancers: Current insights and future directions,” Semin Diagn Pathol, 5, 305 (2022). PMID: 35872032.
AI Fernandez et al., “Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue, JAMA Oncol, 8, 1 (2022). PMID: 35113160.
USCAP 2023, “Abstracts: Breast Pathology,” Mod Pathol, Abstracts: 111, 229 (2023). PMID: 35302109.
PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody Package Insert, Roche (2022).