Basal-Like Breast Cancer

Learn about this aggressive breast cancer subtype and how BCRF research is deepening our understanding of it

Breast cancer is a diverse disease that comprises several different subtypes, each with unique biological traits that influence how the cancer grows, spreads, and responds to treatment. Identifying the subtype of breast cancer is important because it guides treatment decisions and helps researchers develop better therapies.

Breast cancers can be classified in two different ways —one used routinely in everyday clinical care, and one used mostly in research or specialized settings. Clinical subtype is determined using standard tests that measure estrogen receptors (ER), progesterone receptors (PR), and HER2. Most patients will hear their cancer described this way. Molecular subtype, though, is based on patterns of gene activity inside the tumor. These molecular subtypes—luminal A, luminal B, HER2-enriched, and basal-like—provide deeper biological insight but are not routinely measured in every patient.

One of the less common but more aggressive molecular subtypes is basal-like breast cancer. While it shares substantial overlap with triple-negative breast cancer (TNBC), basal-like cancer is defined by its molecular and genetic features rather than by standard clinical tests. Researchers continue to study this subtype to better understand why it behaves differently and and to identify targets for therapy  to improve outcomes for patients.

What is basal-like breast cancer?

The term “basal-like” comes from studies that examined the patterns of gene activity inside breast tumors. Researchers found that some tumors have gene expression patterns that resemble those exhibited by basal cells, which form the outer layer of the milk ducts. These tumors are therefore “basal-like” because they are molecularly similar to basal cells.

Basal-like breast cancers are usually:

• Hormone receptor (HR)-negative: They lack estrogen receptors (ER) and progesterone receptors (PR).
• HER2-negative: They do not overexpress the HER2 protein.
• High grade: Their cells look very different from normal cells and tend to grow and divide quickly.
• Genomically distinct: They display a particular “basal-like” gene expression profile on molecular tests.

About 15 percent of all breast cancers fall into the basal-like category, and most are triple-negative. However, not all triple-negative tumors are basal-like, and not all basal-like tumors are triple-negative. We explore this distinction further below.

Basal-like cancers, like TNBC, are more common in younger women, Black women, and those who have a BRCA1 mutation. They tend to have higher rates of recurrence and metastasis, especially in the first few years after diagnosis.

Most basal-like breast cancers carry changes in an important gene called TP53, which normally acts as a safeguard to stop damaged cells from dividing. When TP53 is altered, cancer cells grow more quickly and are harder to control, contributing to the fast-growing nature of this subtype.

How is basal-like breast cancer diagnosed?

After the doctor obtains a breast biopsy, he or she will send it for a routine clinical test called immunohistochemistry (IHC). IHC is a staining  technique that can detect tumor-specific factors in a tissue sample, such as the presence of estrogen receptors (ER), progesterone receptors (PR), HER2 protein expression levels, and the percentage of cancer cells positive for Ki-67, a protein that indicates how quickly the cells are dividing. But IHC alone cannot precisely identify basal-like tumors.

Doctors sometimes use it to look for triple-negative cancers that also express proteins such as cytokeratin 5/6 or epidermal growth factor receptor (EGFR), which are also indicative of basal-like breast cancer. But the most accurate way to confirm the basal-like subtype is with a gene expression test such as PAM50 (Prosigna®).

PAM50 tests are used to analyze the activity of 50 genes with the results officially designating a tumor as luminal A, luminal B, HER2-enriched, or basal-like. Because molecular subtyping isn’t used for all patients, many people with basal-like tumors may only hear that they have triple-negative breast cancer. In research and advanced care settings, however, identifying the basal-like subtype can provide more detailed insights.

Basal-like breast cancer vs. triple-negative breast cancer

Triple-negative breast cancer is defined by what it lacks, while basal-like breast cancer is defined by what it has; that is, the genes it expresses. This key difference helps explain why most—but not all—TNBCs are basal-like, and why the two terms are related but not interchangeable.

TNBC is estrogen-, progesterone-, and HER2-negative as identified via IHC staining. Basal-like breast cancer, however, is defined by molecular profiling or examination of the genes expressed in the tumor sample. They show “basal-like” genetic activity, often expressing basal cytokeratin and EGFR, for example. Roughly 70 to 80 percent of TNBCs are basal-like, which means most—but not all—triple-negative tumors are basal-like.

The remaining TNBCs may fall into other gene-expression subtypes that have distinct molecular profiles, and as a result, may have different treatment implications. Conversely, some basal-like cancers may weakly express hormone receptors or HER2 and therefore would not be categorized as TNBC, even though their gene expression profiles may be similar.

The overlap between TNBC and basal-like breast cancer is important. Both tend to be aggressive and likely cannot be targeted with hormone or HER2 therapies. However, ongoing research may reveal why some patients respond differently to treatment and whether basal-like classification can identify and refine therapy decisions.

Basal-like breast cancer treatment

Because most basal-like tumors are triple-negative, treatment approaches are similar to those used for TNBC. These cancers lack hormone receptors and HER2 protein, the targets of hormone or anti-HER2 therapies, so treatment typically consists of surgery, chemotherapy, radiation, and, increasingly, newer targeted drugs.

For early-stage basal-like cancer, surgery (lumpectomy or mastectomy) is often the first step. The doctor will also evaluate the patient’s lymph nodes to see if the cancer has spread. Radiation therapy frequently follows lumpectomy to reduce the risk of recurrence to the breast.

Chemotherapy is a central component of treatment for basal-like breast cancer. These tumors are often sensitive to chemotherapy, but resistance develops and recurrence rates remain high. Other treatments discussed below may be added to chemotherapy or used in specific situations. Common chemotherapy regimens include anthracyclines (like doxorubicin) and taxanes (like paclitaxel). Platinum-based chemotherapy (such as carboplatin or cisplatin) is sometimes used, especially in patients with BRCA1 mutations, since these drugs exploit DNA repair weaknesses in BRCA1-mutated tumor cells.

In recent years, immunotherapy has begun to change the treatment landscape for basal-like and triple-negative breast cancers. Immune checkpoint inhibitors, such as Keytruda® (pembrolizumab), can be used in combination with chemotherapy for some patients with advanced disease or if the cancer is at high risk of recurrence. Immune checkpoint inhibitors show greater success if the tumor expresses PD-L1, a protein that helps cancer cells hide from a person’s immune system.

While hormone and HER2-targeted therapies aren’t used for basal-like breast cancer, other targeted treatments are emerging:

• PARP inhibitors, like Lynparza® (olaparib) and Talzenna® (talazoparib), are approved for patients with inherited BRCA1 or BRCA2 mutations. These drugs target “backup” DNA repair pathways in cells when BRCA1- and BRCA2-mediated DNA repair is not functional because of the mutation.
• Antibody-drug conjugates (ADCs) such as Trodelvy® (sacituzumab govitecan) have shown benefit in metastatic TNBC, including basal-like cases. These drugs deliver chemotherapy directly to the tumor by binding to a protein called Trop2, present on the surface of the cancer cells, and releasing the drug directly to the tumor, sparing healthy cells. Recently, a HER2-specific ADC, Enhertu® (trastuzumab deruxtecan) has shown efficacy in HER2-low cancers, some of which have been thought to be TNBC or basal -like.  

Because treatment options for basal-like breast cancer are more limited compared to luminal cancers, patients are often encouraged to participate in clinical trials. Trials are testing new combinations of chemotherapy, immunotherapy, and targeted agents, as well as vaccines designed to stimulate the immune system against cancer.

Basal-like breast cancer research

Research into basal-like breast cancer is advancing quickly, with several main goals. Scientists are studying why basal-like cancers are so aggressive and how they specifically differ from other triple-negative tumors. They are probing the basic biology of the disease to discover why basal-like breast cancer becomes resistant to treatment, spreads more readily, and is harder to treat with standard therapies. For example, they are looking at DNA repair deficiencies that may be exploited; determining if the tumor cell resembles stem cells, which are involved in tumor initiation; and studying the immune evasion strategies the tumors may deploy.

One challenge is ensuring accurate distinction between basal-like and other TNBC subtypes. Researchers are working to standardize molecular testing and integrate it into clinical care so that subtyping provides actionable treatment information.

Basal-like tumors can develop resistance to chemotherapy, so researchers are investigating the following alternatives:

• combination therapies that pair chemotherapy with immunotherapy, PARP inhibitors, or CDK4/6 inhibitors, which block proteins that drive cell division and are being investigated for use beyond ER-positive breast cancer
• targeting DNA damage response pathways, which may be especially effective in BRCA-mutated or other tumors where the DNA repair machinery is faulty
• exploiting tumor metabolism or vulnerabilities in basal-like cell signaling pathways

While immunotherapy has shown promise, not all basal-like tumors respond. Some current trials aim to identify biological signatures that predict which patients may benefit. Others test new strategies, such as cancer vaccines or drug combinations that may make tumors more “visible” to the immune system.

Circulating tumor DNA (ctDNA) tests, which analyze fragments of tumor DNA found in the blood, are being studied as a way to detect evidence of cancer remaining after treatment (called minimal residual disease) or recurrence earlier than imaging tests would. This approach could allow doctors to tailor treatment in real time, escalating therapy for patients at risk of relapse or sparing others unnecessary side effects.

Basal-like breast cancer is a rare but aggressive subtype that often overlaps with key characteristics of TNBC. While treatment options have historically been limited to surgery, chemotherapy, and radiation, progress in immunotherapy, PARP inhibitors, and antibody-drug conjugates are offering new hope.

Research continues to push forward, with scientists working to uncover the unique biology of basal-like cancers and find more effective therapies with less severe side effects. For patients, this means that while the diagnosis can feel daunting, advances in science and clinical care are steadily improving options and outcomes.