Luminal B Breast Cancer Explained

BCRF outlines the mechanisms of this breast cancer subtype, how experts diagnose and treat luminal B breast cancer, and how research is improving outcomes

Breast cancer is not a single disease. It comes in many forms, each with unique characteristics that affect how it grows, spreads, and responds to treatment. Understanding the specific type of breast cancer you have can help your doctors choose the most effective care plan.

One specific type is luminal B breast cancer. It’s less common than luminal A, but often more aggressive. Personalizing breast cancer treatment for patients with luminal B is an important goal as researchers seek to uncover better ways to detect and treat it.

Read on to learn how luminal B breast cancer is different from other subtypes, how it’s diagnosed and treat, and how research is uncovering new insights to improve treatment.

What is luminal B breast cancer?

The term “luminal” refers to how the cancer cells resemble the inner (luminal) cells that line the milk ducts of the breast. Luminal cell growth and activity are strongly regulated by hormone signaling. Because of this, luminal cells naturally express estrogen receptors (ER) and often progesterone receptors (PR). When cancers arise from these luminal cells, they usually retain that hormone receptor expression, which is why luminal subtypes (A and B) are hormone receptor (HR)–positive breast cancers. Approximately 15 to 20 percent of tumors are classified as luminal B.

Luminal B tumors are characterized by high levels of ER, but they are more likely than luminal A to be PR-negative. They may also be HER2-positive, meaning they overexpress the HER2 protein. About 10 to 20 percent of luminal B tumors are HER2-positive. They may also have higher levels of Ki-67 protein, a highly accurate indicator of rapid cell growth. Luminal B tumors therefore tend to grow faster, have a higher tumor grade, and carry a higher risk of the cancer returning (recurrence).

Because luminal B cancers typically have lower levels of HR expression compared to luminal A, they may not respond as well to hormone therapy. However, they are more likely to respond to chemotherapy. Since luminal B tumors may also be HER2-positive, treatment plans may include drugs that target HER2 specifically in addition to hormone therapy.

While luminal A cancers are often described as having a “slower-growing” biology, luminal B cancers tend to fall somewhere between luminal A and more aggressive subtypes like HER2-enriched or triple-negative breast cancer.

The more aggressive a breast cancer is, the more intensive the treatment plan. So, patients with luminal B tumors may require more intensive treatment compared to patients with luminal A tumors. HR-positive/HER2-positive breast cancers (sometimes called triple-positive breast cancers) are often treated more aggressively than HER2-negative luminal B cancers.

How is luminal B breast cancer diagnosed?

Doctors can determine breast cancer subtypes by testing tumor tissue samples. The primary test used in clinical settings is immunohistochemistry staining (IHC), which detects the presence of estrogen receptors, progesterone receptors, HER2, and the proliferation marker Ki-67.

Luminal B tumors typically have a higher Ki-67 score than luminal A. This elevated proliferation rate helps distinguish luminal B breast cancer and informs treatment decisions, but Ki-67 score alone doesn’t definitively classify luminal B breast cancer. While cutoff values can vary by institution, higher scores generally indicate a greater risk of recurrence and the potential need for chemotherapy.

In addition to IHC testing, other genomic tests can help confirm subtype classification by analyzing expression levels of specific genes. These tests, such as the PAM50 assay (Prosigna^®), are performed on tumor samples with the activity levels of certain genes predicting how likely cancer will return after treatment.

Multigene assays such as Oncotype DX^® and MammaPrint^® do not assign subtypes but can help guide decisions about whether a patient will benefit from chemotherapy. Oncotype DX is typically used only in HER2-negative breast cancers, while Prosigna is most often applied to ER-positive, HER2-negative cases. Another test, the Breast Cancer Index^®, can be used to predict risk of cancer returning after five years and can indicate whether extending hormone therapy beyond this point is likely to be beneficial in women with early-stage, HR-positive, HER2-negative breast cancer. 

It’s worth noting that molecular subtyping is not always discussed with patients unless the patient is diagnosed with metastatic breast cancer or is being evaluated for a clinical trial. In everyday care, most oncologists focus on the factors discussed below to guide treatment.

Luminal B breast cancer treatment

Treatment for luminal B breast cancer depends on several factors, including tumor size and stage, lymph node involvement, HER2 status, and menopausal status. As with many breast cancers, surgery is typically the first step: either a lumpectomy or mastectomy. Radiation therapy is usually recommended after lumpectomy, especially if there is a risk the cancer could return to the same area.

Since luminal B cancers are most often HR-positive, hormone therapy plays a central role. This may include:

• Tamoxifen (Nolvadex^®), often prescribed to premenopausal women
• Aromatase inhibitors, which are often used for postmenopausal women
• Ovarian suppression for younger women at higher risk. Estrogen production by the ovaries can be suppressed either temporarily through medication or permanently via surgical removal.

These therapies work by either lowering hormone levels or blocking hormones from binding to their receptors in cancer cells, helping to prevent recurrence.

Unlike many luminal A cancers, luminal B tumors are more likely to require chemotherapy, especially if they are large, have a high tumor grade, or have spread to the lymph nodes. Chemotherapy is particularly likely if the tumor shows a high Ki-67 score or an unfavorable recurrence risk score from genomic testing.

If the tumor is also HER2-positive, HER2-targeted therapies such as trastuzumab (Herceptin^®) and pertuzumab (Perjeta^®) may be added to chemotherapy and hormone therapy. These drugs block HER2 signaling pathways that drive cancer growth.

In some cases—especially for patients with advanced or metastatic disease—CDK4/6 inhibitors like palbociclib (Ibrance^®), ribociclib (Kisqali^®), or abemaciclib (Verzenio^®) may be used alongside hormone therapy. These medications slow cancer cell growth by blocking enzymes involved in cell division and have become cornerstones of treatment for many HR-positive cancers.

In postmenopausal women, especially those at higher risk of recurrence, osteoporosis may be an issue, and doctors may recommend bone-modifying agents to protect bone health and reduce the risk of metastasis to bones.

Luminal B breast cancer research

Researchers are studying luminal B breast cancer to better understand its biology and identify more effective treatments. One of the key challenges is that lumina b tumors are biologically diverse. Some are HER2-positive, some are not. Some respond well to hormone therapy, others less so.

As a result, the research is focused on how to fine-tune therapies based on a tumor’s unique genetic and molecular profile. For example, clinical trials are investigating when chemotherapy or additional therapies can be safely omitted for patients with lower-risk luminal B breast cancers, and when more aggressive treatment is warranted.

Studies are also exploring how to more accurately distinguish luminal A from luminal B, especially when traditional testing methods provide ambiguous results. Improving the consistency of Ki-67 testing within and between institutions and integrating molecular profiling into routine care could help ensure patients receive the right level of treatment.

While hormone therapy is the go-to treatment, some luminal B tumors develop resistance. Research is focusing on combinations of hormone therapy with other targeted agents—such as PI3K inhibitors, CDK4/6 inhibitors, or oral selective estrogen receptor degraders (SERDs)—to overcome resistance and extend remission.

Like luminal A, luminal B cancers generally have low levels of immune cells in the tumor microenvironment and are not highly responsive to immunotherapy. However, scientists are exploring ways to change that by using drugs that modify the tumor microenvironment or make the cancer cells more susceptible to attack from the immune system.

In the metastatic setting, researchers are investigating how to predict and prevent resistance to treatment. Liquid biopsies, genomic sequencing, and real-time monitoring of tumor evolution are opening the door to more personalized, adaptive approaches. One promising example is circulating tumor DNA (ctDNA) testing, a type of liquid biopsy. This testing may allow doctors to detect minimal residual disease or recurrence earlier than imaging and may even monitor response to treatment.

Luminal B breast cancer may be more complex and aggressive than luminal A, but that doesn’t mean there isn’t hope. With early detection, individualized treatment, and advances in research, outcomes are improving. Ongoing clinical trials and scientific discoveries are pushing the boundaries of what’s possible, bringing us closer to a future where every person receives the right treatment, in the right place, at the right time.