Luminal A Breast Cancer Explained

About the most common breast cancer subtype, how luminal A breast cancer is diagnosed and treated, and how research is improving outcomes

Every breast cancer tumor has a unique biological fingerprint that can affect how fast it grows, how it responds to treatment, and how likely it is to return (recurrence). The most common, and often most treatable, is luminal A breast cancer. While luminal A breast cancer is associated with better outcomes, questions still remain: Who is at risk for recurrence? What causes treatment resistance? And how can more patients remain cancer-free?

Thanks to advances in research and precision medicine, scientists and clinicians are working to answer those questions. Read on to learn what sets luminal A breast cancer apart from other subtypes, how it’s diagnosed and treated, and how research is unlocking new ways to improve outcomes.

What is luminal A breast cancer?

When a patient is diagnosed with breast cancer, doctors determine the tumor’s size, stage, and grade. They also classify it based on hormone receptor (estrogen and progesterone) and HER2 status. But breast tumors can also be classified by molecular subtype, which provides additional information about their biology and creates a more detailed picture of the cancer.

Depending on the tumor, a specific gene within its cells may be more or less “turned on” compared to the same genes in other cells. This is called gene expression. Examining gene expression patterns allows researchers to paint a “molecular portrait” of each tumor. Through this process, investigators have been able to classify breast cancer into four distinct molecular subtypes: luminal A, luminal B, HER2-enriched, and basal-like.

Luminal A accounts for about 50 to 60 percent of breast cancers. Luminal A breast cancers are characterized by higher levels of the estrogen receptor (ER) and lower levels of the Ki-67 gene, an established indicator of how quickly cells grow and divide to make new cells. They tend to be progesterone receptor (PR)–positive and HER2-negative and are more likely to be lower grade, meaning that the tumor cells look more like normal breast cells. Luminal A tumors differ from luminal B tumors, which are also ER-positive but often have higher levels of Ki-67 and lower levels of PR, and may be HER2-positive. Luminal B breast cancers tend to grow faster and have a worse prognosis than luminal A.

Because luminal A tumors typically respond well to hormone therapy, they tend to have the best prognosis of the four subtypes. And because they have lower Ki-67 levels, they grow more slowly and have a reduced risk of recurrence. As such, patients with this subtype have the highest survival rate.

How is luminal A breast cancer diagnosed?

While molecular subtypes like luminal A are important in research and help guide new treatment strategies, most patients are not routinely told their molecular subtype—especially when they have early-stage breast cancer. Instead, your doctor will focus on other key factors like hormone receptor status, HER2 status, and tumor grade to determine the best treatment plan. Molecular subtyping may be more relevant in metastatic cases or when being evaluated for a clinical trial.

Luminal A breast cancer is diagnosed using immunohistochemistry (IHC) staining on a breast biopsy sample. IHC testing helps pathologists determine subtypes of cancer by looking for unique tumor markers within cancer cells.

The IHC test uses antibodies—specialized proteins that bind specific markers on cancer cells—to help identify the tumor’s characteristics. When these antibodies attach to their targets, they produce a visible stain that shows whether certain markers are present. To help identify luminal A breast cancer, pathologists look for staining that shows estrogen and progesterone receptors are present. Luminal A tumors typically show strong staining for both estrogen and progesterone receptors.

The test also checks for HER2, another important marker. Results are scored from 0 to 3 based on how much HER2 protein is present; luminal A tumors typically score 0 or 1. Luminal A tumors tend to have a low score on the Ki-67 index, a test that estimates how quickly cancer cells are growing.

In addition to IHC testing, other tests can be performed. The PAM50 assay (Prosigna®) can confirm luminal A classification by analyzing expression levels of specific genes and multigene assays such as Oncotype DX® and Mammaprint® can help guide decisions about whether a patient will benefit from chemotherapy.

Luminal A breast cancer treatment

Treatment for luminal A breast cancer may involve a mix of local therapy, such as surgery or radiation, and systemic therapy, such as hormone therapy or chemotherapy.

Because luminal A breast cancer is hormone receptor–positive and depends on estrogen to grow, it responds well to hormone therapy—a form of targeted therapy. This is not the same as hormone replacement therapy (HRT), which is sometimes used to address symptoms related to menopause. Hormone therapy works by either lowering estrogen levels or by blocking the hormone from binding to its receptor. Both actions prevent estrogen from signaling to cancer cells to keep growing.

In premenopausal women, the ovaries are the main source of estrogen, so ovarian suppression is an important strategy for reducing estrogen production. There are two main approaches to ovarian suppression:

• Temporary suppression using medications such as gonadotropin-releasing hormone (GnRH) agonists, like goserelin (Zoladex®) or leuprolide (Lupron®). These turn off the ovaries’ hormone production.
• Permanent suppression via surgical removal of the ovaries (oophorectomy) or ovarian radiation. This halts estrogen production altogether.

Ovarian suppression is often used in combination with other hormone therapies especially in younger women who are high-risk or who have advanced hormone receptor–positive breast cancer.

Aromatase inhibitors, another kind of hormone therapy, work by specifically preventing the enzyme aromatase from converting androgen hormone into estrogen. They include anastrazole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®).

Other types of hormone therapy prevent estrogen from encouraging cancer’s growth by directly acting on the estrogen receptor. Selective estrogen receptor modulators (SERMs), such as tamoxifen (Nolvadex®) and toremifene (Fareston®), bind to and cause structural changes to estrogen receptors, thereby blocking estrogen binding. Selective estrogen receptor degraders (SERDs), like fulvestrant (Faslodex®) and elacestrant (Orserdu®), also interact with estrogen receptors but cause them to actively break down.

More recently, CDK4/6 inhibitors have been approved for metastatic and early-stage hormone receptor–positive breast cancer and may be combined with hormone therapy to delay disease progression and improve survival. These drugs include abemaciclib (Verzenio®), palbociclib (Ibrance®), and ribociclib (Kisqali®). They work by preventing cancer cells from dividing and growing.

Treatment options and regimens can vary depending on the tumor size, grade, and stage as well as any individual health considerations.

Research into luminal A breast cancer

While luminal A breast cancer can be associated with an excellent prognosis, particularly when detected early, research is aiming to improve outcomes further, especially in patients with high-risk or advanced disease.

Over time, hormone receptor–positive breast cancers can develop resistance to hormone therapies, especially if the breast cancer metastasizes or spreads to other parts of the body. Researchers are investigating specific biological processes that contribute to drug resistance, and mutations in the estrogen receptor 1 (ESR1) gene, which can activate the estrogen receptor even in the presence of hormone-blocking therapy.

Another mechanism of resistance involves activation of the PI3K/Akt/mTOR signaling pathway. This can overcome the estrogen-blocking activity of hormone therapy, essentially allowing cells to grow without estrogen. These discoveries have led to the development of targeted therapies, such as PI3K (alpelisib/Piqray®) and mTOR inhibitors (everolimus/Afinitor®), that can be combined with hormone therapy to help delay disease progression.

Since luminal A tumors can recur 10 or more years after diagnosis, researchers are also focused on understanding this late recurrence and the role of tumor dormancy in the process. Dormant cancer cells can remain undetectable for long periods before reactivating. Efforts are underway to discover how these cells survive and evade treatment, with the ultimate goal of developing therapies to eliminate them before they can cause recurrence.

Another promising area involves liquid biopsy techniques, such as testing for circulating tumor DNA (ctDNA). These blood-based biomarkers may help detect any cells that remain after treatment. Because this test is sensitive, it may help oncologists identify signs of cancer recurrence months before they appear on scans, allowing for earlier intervention.

Researchers are also exploring how to make immunotherapy more effective for luminal A breast cancer. Though it hasn’t shown much benefit in this subtype yet, combining it with other treatments may help the immune system better recognize and respond to cancer cells. Ongoing research is essential to better understand what drives late recurrence, treatment resistance, and individual risk so that therapies can be tailored to each patient’s breast cancer. Scientists are exploring every angle to outsmart this disease. With continued investment in breast cancer research, we can move closer to a future where every person diagnosed with breast cancer can live a longer, healthier life.