HER2-low vs. HER2-negative:
Identifying HER2 expression
Hormone receptors (HR), estrogen receptor (ER) and progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) serve not only as predictive and prognostic biomarkers but also to summarize the biology of three groups of breast cancer: luminal-like (HR-positive and HER2-negative), HER2-positive (HER2+, any HR expression) and triple-negative tumors (HR- and HER2-negative).1 HER2-positive breast cancer is defined as the overexpression of HER2 based on immunohistochemistry (IHC) assay (score 3+) or gene amplification indicated via fluorescence in situ hybridization (ISH) assay on at least one tumor sample, and samples lacking such characteristics have traditionally been classified as HER2-negative.2
However, the binary distinction between HER2-positive and HER2-negative has recently been blurred by the emergence of the latest biomarker subgroup, HER2-low.2 As Maryam Lustberg, MD, MPH, Director of the Center for Breast Cancer and Chief of Breast Medical Oncology at the Yale School of Medicine, explains, “We’ve known about the existence of these tumors for several years, but what’s different is we now have a targeted therapy that’s been shown to be beneficial for HER2-low tumors.” (See The first targeted therapy for HER2-low for information about trastuzumab deruxtecan.)
Challenging to define clinically
HER2-low is defined as a tumor having 1+ or 2+ HER2 expression as assessed by IHC with no amplification of the ERBB2 gene detected via ISH.2 While this appears to be a straightforward classification, it is complicated by the fact that HER2-low expression can change over time.1 HER2-low tumors can become HER2-negative and vice versa, begging the question as to when is the best time to assess for HER2-low.1 Additionally, spatial differences in HER2-low expression within a tumor can occur along with HER2 expression differences between primary and metastatic tumors.1
HER2-negative: Could it actually be HER2-low?
Researchers estimate that about 60% of metastatic breast cancer (mBC) tumors traditionally classified as HER2-negative actually have low levels of HER2 expression.1,2 One explanation: The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines focus on identifying HER2-overexpression as opposed to low HER2 scores, challenging the distinction between HER2-low and HER2-negative tumors.3 In addition, there is the potential for variability in current tests, notes Dr. Lustberg. “In many ways, the antibody test we have now is imperfect and may not be catching all the patients we should,” she says, explaining that “1+” indicates 10 cells out of 100 indicate an antibody signal, leaving a substantial margin for error between HER2-negative and 1+. “Several studies have shown tremendous interobserver variability,” she says.
A recent assessment of surveys from CAP and analytic data from a Yale University study of 18 pathologists reading 170 breast cancer biopsies found poor scoring accuracy for ERBB2 IHC between 0 and 1+.4 In fact, <70% concordance for IHC ERBB2 score 0 vs 1+ was achieved in 19% of cases read by laboratories, according to CAP surveys.4 Minimal expression of HER2 (“faint, barely perceptible expression in <10% of tumor cells”) is allowed in HER2-negative tumors, as currently defined.3 This HER2-“ultralow” group is currently being investigated in clinical trials that could further impact assessment of HER2 expression.1 “There is a lot of work to determine if better tests can better identify patients that we are mislabeling as HER2-negative,” says Dr. Lustberg.
Ensuring prompt diagnosis of HER2-low
Until further data is available, patients with HER2-low status at any time and from any biopsy (primary tumor diagnosis, metastatic biopsy, latest biopsy, etc.) have the potential to benefit from trastuzumab deruxtecan. To identify patients as soon as possible in the course of treatment, Dr. Lustberg offers the following key strategies:
- Carefully document all IHC scoring and biomarkers. Second-line treatment with trastuzumab deruxtecan may be an option for tumors that were HER2-low at any point.5
- Consider obtaining a new metastatic tissue biopsy if it has been a long time since a previous biopsy. Not only can HER2 status can change over time, but pathologists are becoming more aware of HER2-low.
- Be aware of any HER2-low biopsy, even one taken years earlier, and the opportunity for using trastuzumab deruxtecan in the second- or third-line setting. More patients are going to be eligible for this therapy than many physicians realize.
- Note that advanced assays and pathologic criteria are under investigation for greater accuracy in identifying HER2-low patients.
—by Ben Holmes
References
1. Tarantino P, et al. Navigating the HER2-low paradigm in breast oncology: new standards, future horizons. Cancer Discovery. 2022;12(9):2026-2030.
2. Tarantino P, et al. HER2-low breast cancer:
pathological and clinical landscape. J Clin Oncol. 2020;38(17):1951-1962.
3. Wolff AC, 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. Archives of Pathology & Laboratory Medicine. 2018;142(11):1364-1382.
4. Fernandez AI, et al. Examination of low ERBB2 protein expression in breast cancer tissue. JAMA Oncology. 2022;8(4):607-610.
5. U.S. Food and Drug Administration. FDA Approves Fam-trastuzumab Deruxtecan-nxki for HER2-low Breast Cancer. Released August 05, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-low-breast-cancer
Treatment breakthrough:
The first targeted therapy for HER2-low
Researchers estimate that about 60% of metastatic breast cancer (mBC) tumors traditionally classified as HER2-negative actually have low levels of HER2 expression, with most HER2-low cancers being hormone receptor (HR)-positive (65-83%), consisting of luminal subtypes and triple-negative tumors (HR- and HER2-negative).1-3
Yet historically, the significance of this classification was unclear.4 While experts have been aware of the substantial number of patients with HER2-low mBC for some time, how to test for and classify HER2 expression has long been the subject of debate (see Identifying HER2 expression). Perhaps the main reason HER2-low was previously considered largely inconsequential was that until now, there was a lack of therapeutic options.
Indeed, results from a groundbreaking study—the DESTINY-Breast04 trial of trastuzumab deruxtecan—have at long last provided the clinical meaning for HER2-low mBC that so many patients and oncologists had been searching for.5
Trastuzumab deruxtecan: shifting the treatment paradigm
In August 2022 the FDA approved the first and only HER2-targeted therapy, trastuzumab deruxtecan, for treatment of patients with recurrent unresectable or metastatic HER2-low (ICH 1+ or 2+/ISH-) breast cancer in the second-line or later setting, as determined by an FDA-approved test.6
“Approximately two-thirds of HR-positive and one-third of triple-negative patients fall into this HER2-low category, and now they have a whole new treatment option available to them that wasn’t available before,” says Maryam Lustberg, MD, MPH, Director of the Center for Breast Cancer and Chief of Breast Medical Oncology at the Yale School of Medicine.
After approval, NCCN Guidelines released an update that recommends trastuzumab deruxtecan, an antibody-drug conjugate (ADC), as the Category 1 preferred systemic therapy option for patients with HER2-low mBC.7 The FDA-approved indication for second-line therapy includes patients who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.
“Dawn of a new era”
The DESTINY-Breast04 trial evaluated 557 HER2-low patients, 494 (88.7%) with HR-positive disease and 63 (11.3%) with HR-negative disease, who were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice chemotherapy.5 A significant improvement was observed in patients receiving trastuzumab deruxtecan vs. physician’s choice chemotherapy regardless of HR status in both:
- Overall survival (23.4 months vs. 16.8 months; P =.001)
- Median progression-free survival (9.9 months vs.
5.1 months; P <.001).
“I think it’s the dawn of a new era that we essentially have antibody-drug conjugate therapy being used for two big subtypes of breast cancer that didn’t have an option for HER2 targeting,” says Dr. Lustberg. “It’s a paradigm shift for expanding options, and the overall survival benefit was striking. We don’t see these big differences often.”
—by Ben Holmes
References
1. Tarantino P, et al. Navigating the HER2-low paradigm in breast oncology: new standards, future horizons. Cancer Discovery. 2022;12(9):2026-2030.
2. Tarantino P, et al. HER2-low breast cancer:
pathological and clinical landscape. J Clin Oncol. 2020;38(17):1951-1962.
3. Eiger D, et al. The exciting new field of HER2-low breast cancer treatment. Cancers. 2021;13(5):1015.
4. Tarantino P, et al. Prognostic and biologic significance of ERBB2-low expression in early-stage breast cancer. JAMA Oncology. 2022;8(8):1177-1183.
5. Modi S, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. New England Journal of Medicine. 2022;387(1):9-20.
6. U.S. Food and Drug Administration. FDA Approves Fam-trastuzumab Deruxtecan-nxki for HER2-low Breast Cancer. Released August 05, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-low-breast-cancer
7. Gradishar WJ, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Breast Cancer, Version 4.2023. Updated March 23, 2023.
Initiating targeted
therapy for HER2-low:
Patient
education &
monitoring
Antibody-drug conjugates (ADCs) have emerged as a go-to option for many oncologists. As Nicholas P. McAndrew, MD, MSCE, Assistant Clinical Professor of Medicine, Division of Hematology/Oncology, at UCLA David Geffen School of Medicine, explains, “Given the very high response rates seen with modern ADCs, there are few drugs that rival this in the second line and beyond.”
However, as with all medications, it’s crucial to provide patient counseling before initiating any ADC, including trastuzumab deruxtecan. “I think it’s important to highlight how these drugs work and how they are different than standard HER2-targeting antibodies,” notes Dr. McAndrew. ADCs represent a new advancement in the breast cancer landscape in recent years, and even previously treated patients may be unfamiliar with the basic principles of ADC therapy and their anti-cancer effects.1
“I also think, as with any drug, it’s important to discuss toxicity management and specifically counsel on the ILD/pneumonitis risk,” says Dr. McAndrew. Interstitial lung disease (ILD) is a well-described adverse event associated with several HER2-targeting therapies, including ADCs.2
In the DESTINY-Breast04 trial of trastuzumab deruxtecan, the most common drug-related adverse events were nausea (70.3%), fatigue (47.7%) and alopecia (37.7%).3 ILD or pneumonitis occurred in a minority of patients (12.1%). “If we catch ILD symptoms early, we do a temporary hold on the drug and patients tend to recover without any significant issues,” says Maryam Lustberg, MD, MPH, Director of the Center for Breast Cancer and Chief of Breast Medical Oncology at the Yale School of Medicine. Here, Dr. Lustberg describes how she minimizes side effects such as:
- Nausea has been a greater challenge in the real-world setting compared with clinical trials of trastuzumab deruxtecan, notes Dr. Lustberg. Many patients will require multiple agents for adequate control; low-dose olanzapine at night, for example.
- Fatigue is a common concern as it relates to advanced cancer and to treatment with trastuzumab deruxtecan. Ensure proper supportive care—e.g., physical activity and oncologic rehab—and monitor for worsening anemia, thyroid dysfunction and nutritional imbalances.
- Alopecia: Some patients are bothered by hair loss and may want to consider scalp cooling, although limited data are available.
- Respiratory symptoms raise concern for potential ILD, including a worsening cough or decreased exercise tolerance. Monitor respiratory function closely with strategies such as walking oxygen measurements prior to starting therapy and prior to each cycle, having patients monitor blood oxygen saturation at home, reviewing routine scans such as CT for “ground glass” changes, etc.
Adds Dr. McAndrew: “I make sure to discuss with patients that it’s important to let me know of any changes in their breathing, even if relatively mild, so we can assess it right away and potentially start steroid treatment.”
—by Ben Holmes and Morgan Meissner
References
1. Koster KL, et al. New antibody-drug conjugates (ADCs) in breast cancer: an overview of ADCs recently approved and in later stages of development. Explor Target Antitumor Ther. 2022;3(1):27-36.
2. Hackshaw MD, et al. Incidence of pneumonitis/interstitial lung disease induced by HER2-targeting therapy for HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2020;183(1):23-39.
3. Modi S, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. New England Journal of Medicine. 2022;387(1):9-20.
Helping your patients with metastatic breast cancer thrive
Here, Lillie D. Shockney, RN, BS, MAS, HON-ONN-CG, University Distinguished Service Professor of Breast Cancer; Professor of Surgery, Johns Hopkins University School of Medicine; and Co-Founder, Academy of Oncology Nurse & Patient Navigators, shares insights gleaned from her more than 35-year career as an oncology nurse and advocate for patients with breast cancer.
Today, approximately 70% of patients with stage IV breast cancer have HR+/HER2-receptors. With improvements in science and the power of medicine, there are new drugs and drug categories that enable a patient to live far longer than they used to, especially if they have these cancer cell features. We have recently learned more about the HER2-receptor. For three decades, we have scored it as being either positive or negative without any middle ground. Now we know there is benefit in looking more strategically at the HER2 score. It may very well be “a little positive” and classified now as HER2-low. This opens up more treatment options for the patient.
But no matter what treatment you and your patient choose, we want them to thrive, enjoying their lives and feeling productive. With more metastatic breast cancer patients living longer, patient-centered communication and shared decision-making are imperative to improve care and quality of life. The Make Your Dialogue Count survey explored emotional needs of patients between initial diagnosis of their stage IV disease and treatment change.1 Some patients’ attitudes and feelings adapted as their disease advanced. Fewer patients reported fear of the unknown (58% vs. 44%) and distress over believing something could have been done to prevent disease progression (26% vs. 12%), but more patients reported hope of keeping the disease stable (46% vs. 59%) and confidence in treatment options (29% vs. 37%).
However, more patients with children ≤17 years old were distressed because they believed something could have been done to prevent disease progression vs. those who had older children or no children. There were instances of disjointedness between patient expectations and what oncologists actually discussed with patients.1
These findings suggest that patients exhibit an ability to adapt during their disease. Having a shared understanding of their concerns and needs strengthens the patient-oncologist partnership and creates a framework for oncologists to tailor disease management and coping strategies to improve quality of life for each patient.
Based on research and my experience with patients (as well as being a two-time breast cancer survivor myself), here are some ways you can help your patients with metastatic breast cancer make the most of their life, regardless of where they are in their cancer journey.
Emphasize a “thriving” mindset. Tell patients that cancer only deserves the time required to keep it in control. They shouldn't let it consume their lives. If they are constantly thinking about their cancer, they are not enjoying their time here and now. Encourage patients to find distractions, such as doing a favorite hobby, reading a book or visiting a friend.
Patients also need to establish ground rules about what people can ask them and when. If they are constantly being asked about their cancer, then distraction won’t work. They might establish a time of the week for family to ask questions about their cancer and its management. Patients need to tell their family and friends to treat them normally and not just see them as someone with cancer. They play many roles—a spouse, a parent, an adult child and sibling, a friend, a colleague and so on. Patients don't want their life to revolve around cancer.
Treat arthralgia. Patients understandably fear disease progression. Research shows most breast cancer survivors have reported arthralgia—which is especially distressing since patients fear these pains are caused by bone metastasis. A key finding: Controlling arthralgia with effective pain management also decreased patients’ fear of the disease possibly spreading.2,3 We don’t want our patients constantly doing an inventory of their body assuming that any ache or pain is related to cancer progression. However, we need to assess their symptoms and determine if additional scans are needed to determine the cause of arthralgia.
Help them connect with others who understand. Metastatic breast cancer patients often don’t fit into a regular support group, and individuals with early-stage disease may treat them with fear, worrying that they will one day join them. It’s important that patients join a group specifically for metastatic breast cancer patients. Some cancer centers offer these and there are also some online. They can try different ones to see what works best for them.
You can also refer patients to a metastatic breast cancer retreat, which are free to attend, although they usually have to provide their own transportation. These retreats were first developed at Johns Hopkins, and now other breast centers are also holding them.3 A metastatic breast cancer retreat is a great opportunity to network with others, learn about new treatments, receive stress management training and make time for laughter and serious discussions, too. Johns Hopkins permits patients from anywhere to attend the retreat as long as they meet the criteria; for more information, email me at shockli@jhmi.edu. For information about retreats elsewhere, contact the National Breast Cancer Foundation.
Give them tools to deal with insensitive people. Patients can have difficulty being understood by coworkers, friends and sometimes family members because they may not “look” sick. We need to make sure that the immediate family grasps the patient's clinical situation, and we should offer tools for how to talk with friends and coworkers. People who mean well can say dumb things. Examples: “You look like you are doing fine. Your cancer is gone, right?” Or, “If you are just taking pills, then this isn’t stage IV because then you would be getting I.V. treatments.” Patients need a script ready with a response to avoid feeling caught off guard (asking others in their support group how they respond can give them ideas). While they can always ignore a person if they feel angry, in cases where they feel it would be useful to educate them, the script will come in handy.
Ask about their goals. Patients want to actively participate in decisions about their treatment, so partnering with the patient is key. We should always be asking these questions at each visit:
- How much do you know about your metastatic breast cancer currently?
- How much do you want to know about your cancer right now?
- What are you currently hoping for?
- What are you most worried about right now?
- What is most important to you now?
- Tell me three things that bring you joy. (Even their joys may change over time.)
Be open and honest. The most important thing a patient wants from their oncologist is honesty. They will likely ask about their longevity. Holding their hand and asking questions, particularly what they are worrying about today and currently hoping for, are critical to do every time you talk with a patient. Don’t tell them how sorry you are for them. Instead, strive to help patients thrive for as long as possible, fulfilling their life goals as they arise.
Teach your patients this: Don’t postpone joy. Patients may say they want to take their family to Disney World in a year or two. If you anticipate they may not be well enough to enjoy such a rigorous adventure, and they can afford to go sooner, give them a drug holiday and have them go now. The patient's family will enjoy seeing photos of their loved one enjoying themselves rather than being wheelchair bound or worse, spending their time in the hotel room because they were too sick to accompany their family to the Magic Kingdom.
References
1. Brufsky AM, et al. Understanding the needs of patients with metastatic breast cancer: Results of the Make Your Dialogue Count Survey. Breast J. 2017;23(1):17-25.
2. Lopez C, et al. Relations between arthralgia and fear
of recurrence: results of a cross-sectional study of breast cancer patients retreated with adjuvant aromatase inhibitors therapy. Support Care Cancer. 2015;23(12):3581-3588.
3. Shockney LD. Fulfilling Hope: Supporting the Needs of Patients with Advanced Cancers. July 2014. Nova Science Publishers; Hauppauge, NY.
Case Study
PATIENT: CINDY, 60, WAS FIRST DIAGNOSED WITH HER2-NEGATIVE METASTATIC DISEASE CONFIRMED BY BIOPSY. ABOUT 5 YEARS LATER, REPEAT METASTATIC SITE BIOPSY CONFIRMED DIAGNOSIS OF HER2-LOW.
“With HER2-low therapy, Cindy is traveling and has an excellent quality of life”
PHYSICIAN:
Maryam Lustberg, MD, MPH
Director of the Center for Breast Cancer and Chief of Breast Medical Oncology at Yale School of Medicine
History:
Cindy was first diagnosed with stage II breast cancer pT2N2M0, ER+99%, PR+99%, HER2 0 invasive lobular right breast s/p mastectomy with TRAM recon in 2000. She started doxorubicin/cyclophosphamide followed by paclitaxel adjuvant chemotherapy. She subsequently had PMXRT and took 5 years of tamoxifen, which was completed in 2006, and transitioned to anastrozole for another 5 years.
She did well until 2017, when she presented with right axilla swelling and arm pain. Imaging revealed brachial plexus cancer recurrence and evidence of osseous metastasis, which was confirmed by biopsy to be consistent with original breast primary with same biomarkers as before. Cindy was initiated on a series of endocrine therapies including fulvestrant/palbociclib; alpelisib/exemestane; and an oral SERD clinical trial. Total duration of these targeted therapies was approximately 5 years when PET CT showed evidence of disease progression with new lung metastases, mediastinal lymphadenopathy, progression of osseous mets and brachial plexus. Repeat metastatic site biopsy (mediastinal lymph node) revealed similar biomarkers as before with presence of 1+ HER2 (HER2-low) that previously had been HER2 0 in prior biopsies.
By the time the first therapy for HER2-low, trastuzumab deruxtecan (T-DXd), was approved, Cindy had undergone years of systemic therapy for metastatic breast cancer. She was feeling fatigued and was worried whether treatment options were running out. She was also having some neuropathy and hand-foot syndrome from the last chemotherapy (capecitabine).
Initiating treatment with T-DXd:
First, Cindy and I reviewed drug-related toxicities in detail. Fatigue, hair loss and nausea are the most common, so I provided a wig prescription and home antiemetic prescription for prochlorperazine. I also reviewed serious but less common toxicities, and we discussed the small risk of interstitial lung disease and what the symptoms may be, including cough, shortness of breath and decreased exercise tolerance.
During cycle 1, Cindy reported nausea symptoms in the first week of therapy that were not fully responsive to the antiemtic. Addition of low-dose olanzapine 5 mg at night on days 1-5 significantly improved these symptoms. After cycle 5, Cindy needed a dose reduction for increasing fatigue, which improved her quality of life and tolerability of treatment.
A year since starting T-DXd, Cindy is still responding to treatment and reports an excellent quality of life. She is traveling between treatment cycles and visiting friends and family. She feels hopeful and very glad that this was an option that was made available to her.
Considerations:
Now that there is an approved therapy for HER2-low, it is very important to consider serial metastatic biopsies, particularly in patients who had HER2 0 classification in older specimens or on bone biopsies, which may yield inaccurate results.
The new indication for T-DXd is an important targeted therapy option for patients with HER2-low tumors. The advent of antibody drug conjugate (ADC) therapy has shown remarkable improvement in clinical outcomes and overall survival advantage. Future research will focus on combination therapies as well as new ADCs to further expand systemic therapy options.
Q&A
Insight on treating HER2-low metastatic breast cancer
Our expert: Melissa McShane, MD, medical oncologist specializing in breast cancer and Assistant Professor, Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia
Q: How is the treatment paradigm changing for patients with HER2-low metastatic breast cancer?
A: The approval of trastuzumab deruxtecan (T-DXd) in the treatment of patients with unresectable or metastatic HER2-low breast cancer has added an additional therapeutic option that these patients weren’t previously a candidate to receive. This includes both hormone receptor (HR)-positive and HR-negative patients who must have received chemotherapy for metastatic disease or have had disease recurrence during or within 6 months after completing adjuvant chemotherapy; patients with HR-positive disease must have received at least one line of endocrine therapy.1 Clinicians are now recategorizing around 60% of their patients that were historically HER2-negative as HER2-low. This provides a large population of patients the opportunity to receive a targeted therapy with progression-free survival (PFS) and overall survival (OS) improvement over single-agent chemotherapy, which was the previous standard of care in this scenario.
Q: What are the current challenges in identifying HER2-low disease?
A: The current methods for determining HER2 status are a major challenge in classifying patients as HER2-low. There needs to be more sensitive and objective assays for determining HER2 expression at low levels. Determining HER2-low status by immunohistochemistry (IHC) is not reproducible between pathologists because it was not designed to distinguish HER2-low disease. A recent study by Fernandez, et al, showed a discordance of 41% amongst pathologists in distinguishing HER2 IHC 0 from HER2 IHC 1 or higher.2 Given the concerns in accurately identifying a score of 0 with IHC, several labs are working on new methods for testing antibody concentrations to maximize sensitivity at lower ranges of HER2 expression. If we can identify HER2-low with better sensitivity, we will be able to offer treatment with T-DXd to more patients who may not have met criteria with standard HER2 testing modalities.
Q: When would you consider retesting a patient to determine if they are a candidate for T-DXd?
A: If a patient’s initial site of metastatic disease was HER2-low and they come to a point in their treatment regimen where T-DXd would be an option, there is no need to re-biopsy given that we have confirmed with previous HER2-low testing. If a patient with progression of disease previously had HER2 IHC 0 (HER2-negative disease), it is reasonable to biopsy an additional metastatic site to assess if there is any HER2 heterogeneity of their metastatic disease or if their biomarkers have changed.
Q: What does the future hold for treatment of HER2-low metastatic breast cancer?
A: A major area of research in the management of HER2-low metastatic breast cancer is identifying the mechanisms of resistance to T-DXd. Better understanding of whether resistance comes from loss of the HER2 target and/or resistance to the payload may help direct future studies looking at combination therapies and optimizing sequencing of therapy.
References
1. Modi S, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9-20.
2. Fernandez AI, et al. Examination of low ERBB2 protein expression in breast cancer tissue. JAMA Oncol.
2022;8:1-4.
Clinical Minute:
Test your knowledge of HER2-low therapy
Special thanks to our medical reviewer:
Maryam Lustberg, MD, MPH
Director of the Center for Breast Cancer and Chief of Breast Medical Oncology at Yale School of Medicine
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