Table of ContentsView AllTable of ContentsReceptor StatusTumor BehaviorRisk FactorsDiagnosisTreatmentSummary
Table of ContentsView All
View All
Table of Contents
Receptor Status
Tumor Behavior
Risk Factors
Diagnosis
Treatment
Summary
Human epidermal growth factor receptor 2 (HER2) proteins are found on the surface of breast cells and are involved in normal cell growth. Too much HER2 protein, however, can cause some types of breast cancer to grow and spread. HER2-positive breast cancers have abnormally high levels of HER2 receptors, whereas HER2-negative breast cancers don’t.
There are a few differences when looking at HER2-positive vs. HER2-negative breast cancers, including the tumor’s risk factors, its biology, and its anticipated aggressiveness. HER2 status, along with a tumor’s hormone status and other factors, helps determine the prognosis and treatment options for breast cancer.
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Why Receptor Status Matters
Breast cancer is not a single disease, and researchers now have the ability to break down breast cancer into different subtypes based on the receptor status of the tumors. Among the variations between different types of breast cancers are the proteins found on cell surfaces, which are involved in tumor growth. These proteins are related to the genetic material of cancer cells.
It’s important to note, however, thatallbreast cells—both cancerous and noncancerous—have HER2 receptors on their surfaces. The difference is that HER2-positive breast cancer cells have 40 to 100 times more receptors than HER2-negative breast cancer cells or normal breast cells. In positive cases, the abundance of receptors fuels the cancer.
By knowing your HER-2 receptor status, your healthcare provider can carefully select the best treatment to stop your breast cancer in its tracks. Options that target HER2 receptors are fruitless if your status is negative—but they are precisely what you need if you are positive.
Verywell / Brianna Gilmartin
How HER2-Positive Cancers Behave
HER2-positive tumors can behave differently in a number of ways.
HER2-positive breast cancers account for 30% of all breast cancers.
Aggressiveness/Tumor Grade
Breast tumors are given atumor gradeat the time of diagnosis based on the appearance of the cells under the microscope. This number describes the aggressiveness of a tumor, with 1 being the least aggressive and 3 being the most aggressive.
HER2-positive tumors are more likely to have a tumor grade of 3.
Spread to Lymph Nodes
Because HER2-positive tumors tend to reach a higher tumor grade, they also tend to grow faster than tumors of a lower grade.HER2-positive breast cancers are more likely to spread tolymph nodes. As such, the stage at diagnosis may also be higher than for HER2-negative tumors, which can impact survival.
Risk of Recurrence: Early and Late
The pattern of breast cancer recurrence may also differ. Small tumors are also more likely to have ametastatic recurrence(in contrast to local or regional recurrence) if they are HER2-positive.
Despite the fact that HER2-positive and estrogen receptor-negative tumors are more likely to recur early on than estrogen receptor-positive and HER2-negative cancers,late recurrences(for example, 10 years later or even further down the road) are much less common.
With estrogen receptor-positive breast cancers, the cancer is more likely to recur after five years than in the first five years; the risk of recurrence remains steady each year for at least 20 years following the diagnosis. In contrast, those who have HER2-positive tumors and reach their five-year mark are much more likely to be “in the clear” and remain recurrence-free.
Metastasis
Whether HER2-positive tumors are more likely to metastasize than negative tumors depends on thesites of breast cancer metastases. The risk of metastases overall, especially brain metastases, is thought to be increased, but many of the studies on this were done prior to the widespread use of Herceptin.
Studies done after the introduction of Herceptin, and other HER2-targeted therapies, have found that HER2-positive breast cancers continue to have a relatively high incidence of brain metastases.HER2-positive tumors tend to spread earlyin the course of the disease to axillary lymph nodes, the lungs, the liver, the bone marrow, the ovaries, and the adrenal glands.
The risk of metastases may also depend on associated factors. For example, the risk ofliver metastases from breast canceris higher with HER2-positive tumors if people also smoke.
Who’s at Risk?
All women have HER2 genes that code for HER2 proteins, which are involved in the growth of breast cells. When too many copies of the HER2 gene are present—due to damage to the genetic material in the cell or mutations—overproduction of HER2 results.
Some people are more likely than others to have HER2-positive breast cancer. Two studies, theLACE studyand thePATHWAYS study, have looked into the characteristics of people who are more likely to be HER2-positive or HER2-negative. What they found was that:
Determining Your HER2 Status
Abreast biopsyis used to determine HER2 status. The biopsy can be sent for laboratory testing with an immunohistochemistry test. The fluorescence in situ hybridization test looks for the HER2 gene in breast cancer cells.
The results of animmunohistochemistrytest show different levels of HER2 positivity. For example, a tumor may be reported as 0, 1+, 2+, or 3+. Tumors with a higher number may be referred to as having anoverexpression of HER2.
According to the American Cancer Society, immunohistochemistry test results should be considered as follows:
With this in mind, you may also be tested for progesterone and estrogen receptors.Triple-negative breast cancersare negative for HER2, estrogen, and progesterone, while triple-positive breast cancers are positive for all three.
The impact of being HER2-positive on breast cancer survival is, of course, a top concern. Unfortunately, statistics can be misleading without considering other aspects of your diagnosis, including cancer stage at diagnosis and whether the tumor is also estrogen and/or progesterone receptor-positive.
Misdiagnosis
It’s also important to mention the heterogeneity of tumors; i.e., one part of a breast tumor may be HER2-positive while another section is HER2-negative. The results you receive will depend on which section of the tumor was sampled in a biopsy.
A misdiagnosis in which a HER2-positive tumor is diagnosed as negative could result in not being offered optimal (targeted HER2) therapy. Of course, being mistakenly diagnosed as HER2-positive if your tumor is HER2-negative could result in using HER2-directed medications, which may be ineffective for you as well. (Note, however, that some HER2-negative tumors have responded to Herceptin, which is the treatment used for HER2-positive tumors.)
Status Changes
It’s also important to know that HER2 status canchange. A tumor that is initially HER2-positive may become HER2 negative if it recurs or spreads. Likewise, a tumor which is initially HER2 negative may become HER2-positive if it recurs. HER2 status should always be retested following a recurrence.
Treatment Options
Treatmentchoices are significantly different for HER2-positive and HER2-negative breast cancers, both for early-stage and metastatic (stage IV) cancers.
People with HER2-positive tumors are less likely to respond tobreast cancer chemotherapythan those who are negative.
Early-Stage Tumors
Prior to the development of targeted therapies for HER2-positive breast cancer, such as Herceptin, the treatment response for people with HER2-positive breast cancer was not as good for those with HER2-negative disease.
Targeted therapy for HER2-positive breast cancerhas changed the prognosis, and now treatment outcomes are essentially the same as for HER2-negative tumors (though HER2-positive tumors tend to be larger).These medications have changed the prognosis for stage I to stage III HER2-positive breast cancer from poor to good.
Herceptin reduces the risk of recurrence and improves 10-year survival rates for those with stage I to stage III disease.There is, however, a greater risk of relapse and metastasis with a positive HER2 status, and survival rates are somewhat lower than for HER2-negative but estrogen receptor-positive tumors.
Does HER2-negative need chemotherapy?Chemotherapy is a treatment option for both HER2-positive and HER2-negative breast cancers, but not everyone with HER2-negative breast cancer requires chemotherapy.
Does HER2-negative need chemotherapy?
Chemotherapy is a treatment option for both HER2-positive and HER2-negative breast cancers, but not everyone with HER2-negative breast cancer requires chemotherapy.
Metastatic HER2-Positive Cancers
There are also differences in the best treatments for HER2-negative cancers and thetreatments for metastatic HER2-positive tumors. As with early-stage tumors, HER2-targeted therapies often improve survival, whereas anti-estrogen therapies are often ineffective. These tumors may also respond differently to treatments ranging from chemotherapy toimmunotherapy drugs.
What foods should I avoid if I’m HER2-positive?Some research suggestsavoiding these foodsif you have HER2-positive breast cancer:White breadsSugary foodsAlcoholRed meatSaturated fats
What foods should I avoid if I’m HER2-positive?
Some research suggestsavoiding these foodsif you have HER2-positive breast cancer:White breadsSugary foodsAlcoholRed meatSaturated fats
Some research suggestsavoiding these foodsif you have HER2-positive breast cancer:
HER2-positive breast cancer involves an overproduction of HER2 proteins, which can cause faster tumor growth and a greater likelihood of spreading to lymph nodes and other areas. This type tends to be more aggressive than HER2-negative cancer, but targeted treatments like Herceptin have improved outcomes, especially for early-stage cases. HER2 status, identified via biopsy, helps doctors choose the best treatments, as HER2-positive cancers respond well to specific therapies.
HER2-positive tumors also have a higher risk of metastasis, particularly to organs like the brain, liver, and lungs. HER2 status can change, so retesting after a recurrence is often recommended. Treatment options differ greatly for HER2-positive and HER2-negative cases, and using HER2-specific therapies has boosted survival rates and helped many patients manage this more aggressive cancer effectively.
23 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Iqbal N, Iqbal N.Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications.Mol Biol Int.2014:852748. doi:10.1155/2014/852748National Cancer Institute.HER2 genetic link to breast cancer spurs development of new treatments.Gonzalez-Angulo AM, Litton JK, Broglio KR, et al.High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller.J Clin Oncol. 2009;27(34):5700-6. doi:10.1200/JCO.2009.23.2025Chumsri S, Li Z, Serie DJ, et al.Incidence of late relapses in patients with HER2-positive breast cancer receiving adjuvant trastuzumab: Combined analysis of NCCTG N9831 (alliance) and NRG Oncology/NSABP B-31.J Clin Oncol. 2019;JCO1900443. doi:10.1200/JCO.19.00443Pan H, Gray R, Braybrooke, J, et al.20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.The New England Journal of Medicine. 2017;377:1836-1846. doi:10.1056/NEJMoa1701830Hedayatizadeh-Omran A, Rafiei A, Alizadeh-Navaei R, et al.Role of HER2 in brain metastasis of breast cancer: a systematic review and meta-analysis.Asian Pac J Cancer Prev.2015;16(4):1431-4. doi:10.7314/APJCP.2015.16.4.1431Buonomo OC, Caredda E, Portarena I, et al.New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes.PLoS ONE. 2017;12(9):e0184680. doi:10.1371/journal.pone.0184680Huszno J, Nowara E.Risk factors for disease progression in HER2-positive breast cancer patients based on the location of metastases.Prz Menopauzalny. 2015;14(3):173-7. doi:10.5114/pm.2015.54341Kwan ML, Kushi LH, Weltzien E, et al.Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors.Breast Cancer Res. 2009;11(3):R31. doi:10.1186/bcr2261Ellingjord-Dale M, Vos L, Hjerkind KV, et al.Alcohol, physical activity, smoking, and breast cancer subtypes in a large, nested case-control study from the Norwegian Breast Cancer Screening Program.Cancer Epidemiol Biomarkers Prev.2017;26(12):1736-1744. doi:10.1158/1055-9965.EPI-17-0611Ottini L, Capalbo C, Rizzolo P, et al.HER2-positive male breast cancer: an update.Breast Cancer (Dove Med Press). 2010;2:45-58. doi:10.2147/BCTT.S6519Garcia Hernandez I, Canavati Marcos M, Garza Montemayor M, Lopez Sotomayor D, Pineda Ochoa D, Gomez Macias GS.Her-2 positive mucinous carcinoma breast cancer, case report.Int J Surg Case Rep. 2018;42:242-246. doi:10.1016/j.ijscr.2017.12.025Zangouri V, Akrami M, Tahmasebi S, Talei A, Ghaeini Hesarooeih A.Medullary breast carcinoma and invasive ductal carcinoma: A review study.Iran J Med Sci. 2018;43(4):365-371.Evans DG, Lalloo F, Howell S, Verhoef S, Woodward ER, Howell A.Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens.Breast Cancer Res Treat. 2016;155(3):597-601. doi:10.1007/s10549-016-3697-zAmerican Cancer Society.Breast cancer HER2 status.Niikura N, Liu J, Hayashi N, et al.Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors.J Clin Oncol. 2012;30(6):593-9. doi:10.1200/JCO.2010.33.8889Mercogliano MF, Bruni S, Mauro FL, Schillaci R.Emerging Targeted Therapies for HER2-Positive Breast Cancer. Cancers (Basel). 2023 Mar 26;15(7):1987. doi: 10.3390/cancers15071987. PMID: 37046648; PMCID: PMC10093019.Breast Cancer Research Foundation.What Is HER2-Positive Breast Cancer?American Cancer Society.Treatment of Breast Cancer Stages I-III.Early Breast Cancer Trialists’ Collaborative group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol. 2021 Aug;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6. PMID: 34339645; PMCID: PMC8324484.Mariana Brandão, Rafael Caparica, Luca Malorni, Aleix Prat, Lisa A. Carey, Martine Piccart.What Is the Real Impact of Estrogen Receptor Status on the Prognosis and Treatment of HER2-Positive Early Breast Cancer?Clinical Cancer Research.Volume 26, Issue 12, 15 June 2020. doi: 10.1158/1078-0432.CCR-19-2612Theodoros Foukakis, Jonas Bergh, Sara A Hurvitz.Deciding when to use adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer.Food and Drug Administration.Enhertu label.
Iqbal N, Iqbal N.Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications.Mol Biol Int.2014:852748. doi:10.1155/2014/852748
National Cancer Institute.HER2 genetic link to breast cancer spurs development of new treatments.
Gonzalez-Angulo AM, Litton JK, Broglio KR, et al.High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller.J Clin Oncol. 2009;27(34):5700-6. doi:10.1200/JCO.2009.23.2025
Chumsri S, Li Z, Serie DJ, et al.Incidence of late relapses in patients with HER2-positive breast cancer receiving adjuvant trastuzumab: Combined analysis of NCCTG N9831 (alliance) and NRG Oncology/NSABP B-31.J Clin Oncol. 2019;JCO1900443. doi:10.1200/JCO.19.00443
Pan H, Gray R, Braybrooke, J, et al.20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.The New England Journal of Medicine. 2017;377:1836-1846. doi:10.1056/NEJMoa1701830
Hedayatizadeh-Omran A, Rafiei A, Alizadeh-Navaei R, et al.Role of HER2 in brain metastasis of breast cancer: a systematic review and meta-analysis.Asian Pac J Cancer Prev.2015;16(4):1431-4. doi:10.7314/APJCP.2015.16.4.1431
Buonomo OC, Caredda E, Portarena I, et al.New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes.PLoS ONE. 2017;12(9):e0184680. doi:10.1371/journal.pone.0184680
Huszno J, Nowara E.Risk factors for disease progression in HER2-positive breast cancer patients based on the location of metastases.Prz Menopauzalny. 2015;14(3):173-7. doi:10.5114/pm.2015.54341
Kwan ML, Kushi LH, Weltzien E, et al.Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors.Breast Cancer Res. 2009;11(3):R31. doi:10.1186/bcr2261
Ellingjord-Dale M, Vos L, Hjerkind KV, et al.Alcohol, physical activity, smoking, and breast cancer subtypes in a large, nested case-control study from the Norwegian Breast Cancer Screening Program.Cancer Epidemiol Biomarkers Prev.2017;26(12):1736-1744. doi:10.1158/1055-9965.EPI-17-0611
Ottini L, Capalbo C, Rizzolo P, et al.HER2-positive male breast cancer: an update.Breast Cancer (Dove Med Press). 2010;2:45-58. doi:10.2147/BCTT.S6519
Garcia Hernandez I, Canavati Marcos M, Garza Montemayor M, Lopez Sotomayor D, Pineda Ochoa D, Gomez Macias GS.Her-2 positive mucinous carcinoma breast cancer, case report.Int J Surg Case Rep. 2018;42:242-246. doi:10.1016/j.ijscr.2017.12.025
Zangouri V, Akrami M, Tahmasebi S, Talei A, Ghaeini Hesarooeih A.Medullary breast carcinoma and invasive ductal carcinoma: A review study.Iran J Med Sci. 2018;43(4):365-371.
Evans DG, Lalloo F, Howell S, Verhoef S, Woodward ER, Howell A.Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens.Breast Cancer Res Treat. 2016;155(3):597-601. doi:10.1007/s10549-016-3697-z
American Cancer Society.Breast cancer HER2 status.
Niikura N, Liu J, Hayashi N, et al.Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors.J Clin Oncol. 2012;30(6):593-9. doi:10.1200/JCO.2010.33.8889
Mercogliano MF, Bruni S, Mauro FL, Schillaci R.Emerging Targeted Therapies for HER2-Positive Breast Cancer. Cancers (Basel). 2023 Mar 26;15(7):1987. doi: 10.3390/cancers15071987. PMID: 37046648; PMCID: PMC10093019.
Breast Cancer Research Foundation.What Is HER2-Positive Breast Cancer?
American Cancer Society.Treatment of Breast Cancer Stages I-III.
Early Breast Cancer Trialists’ Collaborative group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol. 2021 Aug;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6. PMID: 34339645; PMCID: PMC8324484.
Mariana Brandão, Rafael Caparica, Luca Malorni, Aleix Prat, Lisa A. Carey, Martine Piccart.What Is the Real Impact of Estrogen Receptor Status on the Prognosis and Treatment of HER2-Positive Early Breast Cancer?Clinical Cancer Research.Volume 26, Issue 12, 15 June 2020. doi: 10.1158/1078-0432.CCR-19-2612
Theodoros Foukakis, Jonas Bergh, Sara A Hurvitz.Deciding when to use adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer.
Food and Drug Administration.Enhertu label.
Fredholm H, Magnusson K, Lindström LS, et al.Long-term outcome in young women with breast cancer: a population-based study.Breast Cancer Res Treat.2016;160(1):131-143. doi:10.1007/s10549-016-3983-9
Pan H, Gray R, Braybrooke, J, et al.20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years.N Engl J Med. 2017;377:1836-1846. doi:10.1056/NEJMoa1701830
Schettini F, Buono G, Cardalesi C, Desideri I, De Placido S, Del Mastro L.Hormone receptor/human epidermal growth factor receptor 2-positive breast cancer: Where we are now and where we are going.Cancer Treat Rev. 2016;46:20-6. doi:10.1016/j.ctrv.2016.03.012
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