Table of ContentsView AllTable of Contents’Receptor Positive' MeaningHow Common Is It?HER2+ ComparisonER+ ComparisonTriple-Negative ComparisonTreatmentMetastatic CasesDiagnosisPrognosis
Table of ContentsView All
View All
Table of Contents
‘Receptor Positive’ Meaning
How Common Is It?
HER2+ Comparison
ER+ Comparison
Triple-Negative Comparison
Treatment
Metastatic Cases
Diagnosis
Prognosis
There is controversy in the medical community about whether triple-positive breast cancer is a distinctive subtype of the disease. Triple-positive breast cancers appear to act differently than other breast cancers in terms of how the cancer cells behave and how the disease responds to treatment.
Knowing the hormone receptor status of your tumor is important because it will help you and your healthcare provider make the best decisions about treatment.
This article will explain what hormone receptors and HER2 receptors are and how triple-positive breast cancer is different from other types. It will also discuss treatment options and how this type of cancer is diagnosed.
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What Does ‘Receptor Positive’ Mean?
When the hormone estrogen binds to estrogen receptors, it stimulates cell growth. The same thing happens with another hormone, progesterone. With HER2, the growth factors bind to the receptor to stimulate growth.
With triple-positive breast cancer, all of these factors are at play and can affect the treatment and prognosis of the disease.
Prevalence
It’s thought that between 20% to 25% of breast cancers are HER2-positive (in some studies, the range is 15% to 30%).Roughly 70% of breast cancers are estrogen-receptor (ER) positive and progesterone-receptor-positive.
Of cancers that are HER2-positive, around 50% are also ER-positive (however, the expression of the ER can be at lower levels).
Overall, roughly 10% of breast cancer tumors might be considered triple-positive. However, large-scale studies looking at how common these tumors are and who gets them are lacking. It’s also important to know that the extent of estrogen positivity can vary between the tumors.
Breast cancers that are exclusively PR-positive are extremely rare.
Triple-Positive vs. HER2-Positive
Breast cancers that are HER2-positive can vary a lot. In general, tumors that are HER2-positive tend to be:
HER2-positive tumors that are also ER-positive (triple-positive) may behave more like ER-positive tumors and HER2-negativetumors, making them less aggressive and more responsive to hormonal treatment.There are also some similarities between triple-positive andtriple-negative breast cancer.
Triple-Positive vs. ER-Positive
Tumors that are triple-positive tend to be more aggressive than those that are ER-positive alone. Hormonal therapy can be less effective and chemotherapy (at least with early-stage tumors) may not work as well.
Triple-positive breast cancers are also more likely to have positive lymph nodes than cancers that are only ER-positive. This may influence the symptoms of triple-positive breast cancer.
Triple-Positive vs. Triple-Negative
However, that does not appear to be the case. While some triple-positive tumors act more like ER-positive tumors, some tumors have similarities to triple-negative tumors. This includes cancers that:
Treatment Approaches
Cancers that are further along might be treatable with:
Breast cancers that are hormone and/or HER2-positive or triple-positive are typically treated with long-term oral medications, including:
Postmenopausal people still make estrogen, though in smaller quantities than premenopausal people. For this reason, menopausal status should be tested before prescribing hormonal therapies in cases of ER-positive breast tumors.For postmenopausal people, aromatase inhibitors such as Arimidex, Femara), or Aromasin might be recommended.
Studies looking at early breast cancers have found less benefit from HER2-targeted therapieswhen the level of both receptors is high. These are the tumors that act more like ER-positive/HER2-negative (luminal A) tumors.However, the reduced effectiveness of hormonal therapies has been noted.
The interaction between HER2 and ER receptors is called “crosstalk.” This crosstalk might explain why responses to hormonal therapy or HER2-targeted therapy are not always what would be expected.
The crosstalk between HER2 and ER may signal hormonal resistance. In other words, communication between the receptors may make anti-estrogen therapy less effective in triple-positive tumors.
Similarly, the activation of ER signaling (related to being ER-positive) may contribute to resistance to HER2-targeted therapies. This could explain the variability in HER2-positive tumors, some of which respond much better than others to HER2-blocking drugs.
It is thought that using the combination of HER2 therapy (for example, Herceptin) and hormonal therapy (such as Tamoxifen or Faslodex (fulvestrant) may restore some of the ER resistance to hormonal therapy. In addition, somebreast cancer chemotherapyregimens work better or worse for HER2-positive tumors.
HER2-Positive Treatment Options
Metastatic Triple-Positive Cancer
While chemotherapy might not be as beneficial for early-stage disease, it often helps with metastatic disease.
Metastatic triple-positive breast cancer is usually treated differently frommetastatic HER2-positive breast cancer. Unlike tumors that are only HER2-positive, there appears to be much survival benefit to using chemotherapy with HER2-blocking therapy (specifically, trastuzumab).
Diagnosing breast cancer usually starts with imaging tests such as a mammogram,breast MRI, and/ or ultrasound. If these tests show something that looks suspicious, abiopsyis done. A biopsy involves removing a small piece of the tumor so that it can be looked at under a microscope. Seeing the cells more closely will help providers figure out the stage and type of cancer a person has.
Determining the HER2 status and hormone receptor status is done with a lab test called animmunohistochemistry(IHC) test.
Samples of the tumor tissue removed during a biopsy are looked at under a microscope. The results are given a rating of 0 to 3. A score of 0 means that a tumor is HER-negative or HR-negative. A score of 3 confirms that a tumor is positive for HER2 or HR-positive. Scores of 1 and 2 are considered borderline.
In general, the behavior and response of triple-positive breast cancer tumors are similar to estrogen-positive/HER2-negative tumors. A retrospective study done from the California Cancer Registry looked at 123,780 cases of stages 1–3 primary invasive breast cancer in women.
The difference in five-year survival between those with triple-positive tumors and those with estrogen-positive/HER2-negative tumors was less than 1% for stage 1 and 2.2% for stage 2. There was no statistically significant difference in five-year survival between the two subtypes in stage 3.
That said, the potential crosstalk between the HER2 and estrogen receptors may lead to resistance to both hormonal and HER2-directed treatments.
Summary
Triple-positive breast cancers are an uncommon subtype of breast cancer where the tumor is positive for HER2 as well as for estrogen and progesterone receptors.
Hormone status and HER2 status of tumors are diagnosed using an immunohistochemistry test.
In addition to surgery, chemotherapy, and radiation, triple-positive cancers can be treated with hormonal therapies and targeted therapies. However, because of some of the unique aspects of tumors at a cellular level, these therapies might not be as effective.
20 Sources
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