These four results show what breast cancer cells depend on to grow and which treatment is likely to work best [1]. ER- and PR-positive means female hormones help the tumour grow and hormone therapy works; HER2-positive (a score of 3+, or 2+ with a positive FISH test) means anti-HER2 drugs help treatment; and Ki-67 shows how quickly the cells are dividing [1, 2, 4]. None of them on its own is "good" or "bad": together they define your type of breast cancer, and every type has effective treatments [1, 6].
Key points
- ER- or PR-positive means at least 1 in every 100 tumour cells has hormone receptors, and hormones help the tumour grow [1, 2]. In a large analysis, taking tamoxifen for 5 years roughly halved the chance of the cancer coming back in the early years [9].
- HER2 is reported as a score from 0 to 3+: 3+ means positive, 2+ means borderline and needs a FISH test, and 0 and 1+ mean negative [4].
- HER2-low means a score of 1+, or 2+ with a negative FISH test. These tumours count as HER2-negative, but if the cancer ever spreads, a newer drug also works for them [4, 11].
- Ki-67 shows how many of every 100 tumour cells are dividing; a higher number means faster growth. The line between "high" and "low" is not the same in every laboratory, and your doctor weighs it together with the other results [1, 5, 6].
- "Which type is better?" No type is simply good or bad; every type has effective treatment, and the stage of the cancer also matters a great deal [1, 8].
What are these tests and why do they matter?
When a biopsy shows breast cancer, the pathologist usually performs special stains called immunohistochemistry (IHC) on the same sample [1, 2]. These stains show which proteins the cancer cells carry [1, 2].
The results tell your doctor [1]:
- how quickly the cancer is likely to grow;
- how likely it is to spread to other parts of the body;
- which treatments are likely to work best.
These results usually appear in a section of the pathology report headed IHC or Biomarkers. For the rest of the report, see How to read a pathology report.
What do ER-positive and PR-positive mean? What does "ER positive 90%" mean?
Healthy breast cells and many breast cancer cells have "receptors". A receptor is like a lock that the female hormones oestrogen and progesterone fit into, sending the cell a signal to grow [1]. ER is the oestrogen receptor and PR (or PgR) is the progesterone receptor [1]. If a tumour has one or both of these receptors, it is called "hormone receptor-positive" (HR+), which means hormones help it grow. Most ER-positive tumours are also PR-positive [1].
- The percentage: shows how many of every 100 tumour cells have the receptor. "ER positive 90%" means 90 of every 100 cells stained; such a tumour is clearly ER-positive [2].
- Positive or negative: if at least 1 in every 100 cells stains, the tumour is positive; if fewer do, it is negative [2].
- ER low positive: if only 1 to 10 of every 100 cells stain, the report uses this phrase. There is little information on how well hormone therapy works in this group, and your doctor will discuss treatment with you [2].
- Staining intensity (weak, moderate, strong): how darkly the cells stained. Some laboratories combine the percentage and the intensity into one score from 0 to 8 (the Allred score); a score of 3 or more means positive [3].
Why does it matter? Hormone receptor-positive cancer is treated with hormone therapy, that is, tablets such as tamoxifen or letrozole. These drugs block the effect of hormones on the cancer cells or lower the amount of hormone the body makes [1]. In an analysis of 20 studies with more than 20,000 women, taking tamoxifen for 5 years for ER-positive cancer roughly halved the chance of the cancer coming back in the first 5 years and cut the risk of dying of breast cancer by about a third over 15 years; in ER-negative cancer it had almost no effect [9]. Hormone receptor-negative cancer does not respond to hormone therapy and is treated in other ways, such as chemotherapy [1].
What is HER2 on a pathology report? What do HER2-negative, HER2-positive and 2+ mean?
HER2 is a protein on the surface of cells that helps control the growth of breast cells [1]. In some breast cancers there is far too much of it, which drives the cells to grow and divide faster; this is called "HER2-positive" [1]. The HER2 result decides whether anti-HER2 drugs, such as trastuzumab (Herceptin), will help treatment [1].
HER2 is usually measured with IHC staining, and the result is a score from 0 to 3+ [4]:
| What the report says | What it means | What it means for treatment |
|---|---|---|
| HER2: 0 (Negative) | HER2-negative [4] | Anti-HER2 drugs are not used [4] |
| HER2: 0, with membrane staining (HER2-ultralow) | HER2-negative; a little staining is seen on the cell membrane [12] | Matters only if a hormone receptor-positive cancer spreads, for one newer drug [12] |
| HER2: 1+ (Negative) | HER2-negative, of the HER2-low kind [4, 11] | The usual anti-HER2 drugs are not used; if the cancer spreads, a newer drug works [4, 11] |
| HER2: 2+ (Equivocal) | Borderline; a FISH (or ISH) test must be done on the same sample [4] | Until the FISH result is back, it cannot be called positive or negative [4] |
| HER2: 2+; FISH: Not amplified | HER2-negative, of the HER2-low kind [4, 11] | Same as a score of 1+ [4, 11] |
| HER2: 2+; FISH: Amplified | HER2-positive [4] | Anti-HER2 drugs together with other treatments [1, 4] |
| HER2: 3+ (Positive) | HER2-positive; there is a great deal of HER2 protein [1, 4] | Anti-HER2 drugs together with other treatments [1, 4] |
FISH (or ISH) is a test that looks at the HER2 gene in the tumour cells; "amplified" means there are too many copies of the gene and the cancer is HER2-positive [4].
What does HER2-low mean?
Until a few years ago, HER2 was simply "positive" or "negative". Today, HER2-negative tumours with a score of 1+, or 2+ with a negative FISH test, are called "HER2-low" [4, 11]. These tumours have some HER2, but not enough to count as HER2-positive [1].
The difference matters once the cancer has spread to other parts of the body. In two large studies of women with breast cancer that had spread and who had already had other treatments, the drug trastuzumab deruxtecan controlled the disease for longer than standard chemotherapy; in one of the two studies, patients also lived longer [11, 12]. In the second study, tumours with a score of 0 but a little staining on the cell membrane (HER2-ultralow) showed similar results [12].
That is why the difference between a score of 0 and 1+ matters today, and pathologists report it carefully [4]. Even so, HER2-low is not yet a separate official category on pathology reports, and studies have not so far shown that these tumours behave differently from other HER2-negative tumours [4].
What is Ki-67? What does a high Ki-67 mean?
Ki-67 is a protein found only in cells that are dividing [1]. The pathologist counts how many of every 100 tumour cells contain Ki-67 and reports it as a percentage; for example, "Ki-67: 30%" means 30 of every 100 cells are dividing [1, 5]. A high Ki-67 means the cancer cells are dividing quickly [1].
- What does "Ki-67 positive" mean? Unlike ER, Ki-67 is not divided into positive and negative; what matters is the number [5].
- High or low? There is no fixed cut-off for all laboratories, and each laboratory should set its own [6]. An international group of experts says that in stage 1 and 2 hormone receptor-positive, HER2-negative cancers, 5 or less can be considered low and 30 or more high; on their own, numbers in between do not have a clear meaning [5].
- Ki-67 does not decide treatment on its own. Its result can vary a little between laboratories [5]. So your doctor weighs it together with the tumour grade, tumour size, lymph nodes and sometimes genomic tests on the tumour to decide whether chemotherapy is needed [5, 6].
An example report, in plain language
| What the report says | What it means in plain language |
|---|---|
| ER: Positive (90%, strong) | Oestrogen receptor-positive: 90 of every 100 tumour cells stained darkly [2] |
| PR: Positive (40%) | Progesterone receptor-positive too: 40 of every 100 cells [2] |
| HER2: IHC 2+ (equivocal); FISH: not amplified | HER2 was borderline at first and the FISH test did not show extra copies of the HER2 gene; so it is HER2-negative, of the HER2-low kind [4, 11] |
| Ki-67: 25% | 25 of every 100 cells are dividing; a middle value that the doctor interprets together with the other results [5, 6] |
This example means hormone receptor-positive, HER2-negative breast cancer; hormone therapy is the basis of treatment, and the doctor decides on the need for chemotherapy from the other features [1, 6]. Everyone's report is different.
What type of breast cancer do I have? Luminal A, luminal B, HER2-positive and triple-negative
| Group | On the pathology report | How many patients? | Main treatments |
|---|---|---|---|
| Hormone receptor-positive, HER2-negative (luminal A or B) | ER or PR positive; HER2-negative (0, 1+, or 2+ with negative FISH) [2, 4] | About 7 in 10 [7] | Hormone therapy; chemotherapy as well for some patients [1, 6] |
| Hormone receptor-positive, HER2-positive (sometimes called "triple-positive") | ER or PR positive; HER2 3+ or positive FISH [4, 6] | About 1 in 10 [7] | Chemotherapy, anti-HER2 drugs and hormone therapy [1, 6] |
| HER2-positive, hormone receptor-negative | ER and PR negative; HER2-positive [6] | About 1 in 20 [7] | Chemotherapy and anti-HER2 drugs [1, 6] |
| Triple-negative | ER, PR and HER2 all negative [1] | About 1 in 8 [7] | Chemotherapy and sometimes immunotherapy [1, 6] |
The share of each group comes from a study of more than 50,000 women with breast cancer in the United States [7].
Luminal A and luminal B: hormone receptor-positive, HER2-negative cancers fall into two groups of their own [6]. In luminal A, ER and PR are both positive and Ki-67 is low; these tumours usually grow more slowly, and hormone therapy is the most important treatment and is often enough on its own [1, 6]. In luminal B, Ki-67 is high or PR is negative or low; all of these patients have hormone therapy and most have chemotherapy as well [6]. In many centres, a genomic test on the tumour also helps with this decision [6].
Read about the treatment of each group on these pages: Treatment of hormone receptor-positive breast cancer, Treatment of HER2-positive breast cancer and The best treatment for triple-negative breast cancer.
HER2-positive vs negative: which is better? Is ER-positive good or bad?
This is a very common question, but it has no simple "good" or "bad" answer [1, 8].
- ER-positive: in a large study, women with hormone receptor-positive, HER2-negative cancer had the best outcomes [8]; one reason is that hormone therapy gives them an extra effective treatment [9]. But these cancers can come back years later: in a study of more than 60,000 women, after 5 years of hormone therapy had ended, recurrences continued steadily up to 20 years after diagnosis [10]. That is why doctors sometimes continue hormone therapy beyond 5 years, and regular follow-up matters [10].
- HER2-positive: these tumours usually grow faster [1], but anti-HER2 drugs have greatly improved the results of treatment [8]. In the same study, among women whose cancer had already spread at diagnosis, the hormone receptor-positive, HER2-positive group survived even longer than the hormone receptor-positive, HER2-negative group [8].
- Triple-negative: grows faster and is more likely to come back [1]; its main treatment is chemotherapy, sometimes with immunotherapy [1].
- Stage of the cancer: the size of the tumour and whether lymph nodes are involved also have a large effect on the outcome [8].
| Group | Out of every 10 women |
|---|---|
| Hormone receptor-positive, HER2-negative | More than 9 [8] |
| Hormone receptor-positive, HER2-positive | About 9 [8] |
| HER2-positive, hormone receptor-negative | About 8 [8] |
| Triple-negative | Nearly 8 [8] |
These numbers are for women diagnosed between 2010 and 2013 in the United States and include all stages together. Each patient's outlook depends on the stage and features of her own cancer [8]. See Is breast cancer curable?
Frequently asked questions
What does triple-positive (ER, PR and HER2 positive) mean?
It means the tumour has both hormone receptors and a lot of HER2 [1]. Treatment is usually a combination of chemotherapy, anti-HER2 drugs and hormone therapy [1, 6]. See Treatment of HER2-positive breast cancer.
ER-positive but PR-negative: is that bad?
The main decision about hormone therapy rests on ER, and PR is used mostly to predict how the disease will behave [2]. In a large analysis, the benefit of tamoxifen in ER-positive cancer did not depend on PR [9]. A negative or low PR may place the tumour in the luminal B group, and your doctor takes this into account when deciding about chemotherapy [6].
My HER2 result is 2+. Does that mean positive?
Not yet. 2+ means borderline, and a FISH (or ISH) test must be done on the same sample [4]. If FISH is positive (amplified), the cancer is HER2-positive; if it is negative (not amplified), it is HER2-negative, of the HER2-low kind [4, 11]. If the FISH result is not on your report, ask your doctor whether it has been done.
My Ki-67 is 15% or 20%. Is that high?
Can ER, PR or HER2 change later?
Yes, hormone receptor status can change over time. That is why, if the cancer comes back after treatment, another biopsy and new tests may be needed [1].
What does triple-negative mean, and can it be treated?
It means ER, PR and HER2 are all negative [1]. These tumours grow faster and are more likely to come back, but they can be treated: with chemotherapy and sometimes immunotherapy [1]. See The best treatment for triple-negative breast cancer.
Are these tests also done for ductal carcinoma in situ (DCIS)?
ER testing is recommended for DCIS, because it shows whether hormone therapy can lower the risk of a later breast cancer; PR testing is optional in DCIS [2]. See What is DCIS (stage 0 breast cancer)?
Related pages
- How to read a pathology report: what the terms mean
- What is cancer grade? Grade versus stage
- What is DCIS (stage 0 breast cancer)?
- Genetic testing for cancer risk: who should be tested?
- Is breast cancer curable?
- Treatment of hormone receptor-positive breast cancer, treatment of HER2-positive breast cancer and treatment of triple-negative breast cancer
Reporting criteria and evidence (for doctors)
For physicians
ER and PgR (ASCO/CAP 2020). Validated IHC is the standard test for predicting benefit from endocrine therapy. 1–100% of tumour nuclei = ER positive; 1–10% should be reported with the "ER Low Positive" category and the recommended comment (limited data on endocrine therapy benefit); less than 1% = ER negative; report the status of controls for results of 0–10%. PgR is used mainly for prognosis in ER-positive tumours. ER testing of DCIS is recommended; PgR is optional [2]. Allred score (Harvey 1999; 1,982 tumours): a 0–8 scale combining the proportion and intensity of staining; a score greater than 2 (corresponding to as few as 1–10% weakly positive cells) was the ER-positivity cut-off based on DFS with adjuvant endocrine therapy [3].
Endocrine therapy benefit by ER. EBCTCG 2011 (20 trials, 21,457 patients): in ER-positive disease (10,645 patients), 5 years of tamoxifen gave a recurrence RR of 0.53 in years 0–4 and 0.68 in years 5–9; in marginally ER-positive disease (10–19 fmol/mg) RR 0.67; independent of PgR, age, nodal status and chemotherapy; breast cancer mortality about a third lower throughout the first 15 years; little or no effect in ER-negative disease [9]. EBCTCG 2017 (88 trials, 62,923 patients disease-free after 5 years of endocrine therapy): recurrences continued at a steady rate from year 5 to year 20; distant recurrence risk 10–41% depending on TN status and grade; grade and Ki-67 had only moderate independent predictive value, and PgR and HER2 were not predictive [10].
HER2 (ASCO-CAP 2023). The 2018 recommendations were affirmed: IHC 3+ positive, 2+ equivocal and requiring ISH, 0 and 1+ negative. Creating new result categories (HER2-Low, HER2-Ultra-Low) is premature, but carefully distinguishing IHC 0 from 1+ has become clinically relevant because of the DESTINY-Breast04 entry criteria, and a new reporting comment is proposed for it [4]. DESTINY-Breast04 (557 patients with HER2-low metastatic disease after 1 or 2 lines of chemotherapy; 88.7% HR-positive): T-DXd versus physician's choice of chemotherapy, in the HR-positive cohort median PFS 10.1 vs 5.4 months (HR 0.51) and OS 23.9 vs 17.5 months (HR 0.64); ILD or pneumonitis 12.1% (0.8% grade 5) [11]. DESTINY-Breast06 (866 HR-positive patients: 713 HER2-low and 153 HER2-ultralow, i.e. IHC 0 with membrane staining; after at least one line of endocrine therapy and no prior chemotherapy for metastatic disease): median PFS in HER2-low 13.2 vs 8.1 months (HR 0.62; 95% CI 0.52 to 0.75), consistent in the exploratory ultralow group; OS immature; ILD 11.3% [12].
Ki-67 and surrogate subtypes. IKWG 2021: analytical validity is achievable with attention to pre-analytical handling and standardised visual scoring; clinical utility is limited to estimating prognosis in ER-positive/HER2-negative T1–2, N0–1 disease, to identify patients who do not need adjuvant chemotherapy: Ki-67 5% or less, or 30% or more [5]. St Gallen 2013: Luminal A-like (ER and PgR positive, HER2 negative, Ki-67 low) versus Luminal B-like HER2-negative (Ki-67 high or PgR negative/low); Ki-67 below 14% best matched genomic Luminal A, a majority of the panel considered 20% or more clearly "high", and a PgR cut-off of 20% was proposed; values should be laboratory-specific. Treatment: Luminal A-like often endocrine therapy alone; Luminal B-like HER2-negative endocrine therapy for all and chemotherapy for most [6].
Distribution and outcome (SEER). Among 50,571 patients with known status: HR+/HER2− 72.7%, triple-negative 12.2%, HR+/HER2+ 10.3% and HR−/HER2+ 4.6% [7]. Four-year breast cancer-specific survival (diagnosed 2010–2013): 92.5%, 90.3%, 82.7% and 77.0% for HR+/HER2−, HR+/HER2+, HR−/HER2+ and triple-negative respectively; in de novo stage IV, HR+/HER2+ did better than HR+/HER2− (45.5% vs 35.9%) [8].
Scientific evidence
Scientific evidence
4 itemsRelevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials
20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years
Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer
Related cancer types
Related questions
References
12 referencesShow all references, 4 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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