Understanding Advanced Treatment Options for Metastatic Breast Cancer

A Deep Dive into Targeted Therapies for HR+, HER2-low, Triple-Negative, and BRCA-Associated MBC

If you’ve recently been diagnosed with metastatic breast cancer (MBC), it can feel like you’re suddenly thrust into a new world filled with acronyms, treatment decisions, and unfamiliar terminology. One of the most empowering things you can do right now is to begin learning about the tools available to you.

We take a deeper look at four innovative categories of treatment that are changing the landscape of metastatic breast cancer care:

• CDK4/6 inhibitors for hormone receptor-positive (HR+) MBC

• Antibody-drug conjugates like Enhertu and Trodelvy

• Immunotherapies for some triple-negative breast cancers (TNBC)

• PARP inhibitors for people with inherited BRCA mutations

Each of these therapies offers new hope, especially as treatment becomes more personalized based on tumor biology. Let’s break each one down.

CDK4/6 Inhibitors: Targeting Cell Cycle in HR+ MBC

What are they?

CDK4/6 inhibitors are a class of drugs that target two proteins—cyclin-dependent kinases 4 and 6—which are involved in cell division. In many HR+ breast cancers, these proteins are overactive, causing cancer cells to grow uncontrollably.

By blocking CDK4/6, these drugs slow or stop the growth of cancer cells while allowing normal cells to recover.

Common CDK4/6 inhibitors:

• Ibrance (palbociclib)

• Kisqali (ribociclib)

• Verzenio (abemaciclib)

  
  

Who gets them?

These therapies are used in people with hormone receptor-positive, HER2-negative metastatic breast cancer, which is the most common subtype of MBC.

They are typically used in combination with hormone therapy such as letrozole or fulvestrant, especially for those who are newly diagnosed with MBC or whose cancer has recurred after initial endocrine therapy.

What to expect:

CDK4/6 inhibitors are taken orally (as pills), often in 3-week-on, 1-week-off cycles, depending on the specific drug.

Common side effects include:

• Low white blood cell counts (neutropenia)

• Fatigue

• Nausea

• Diarrhea (more common with Verzenio)

• Hair thinning

Routine blood work is important to monitor how your body is responding.

Why they matter:

CDK4/6 inhibitors have significantly extended progression-free survival—and in some cases, overall survival—for patients with HR+ MBC. Kisqali, for example, has shown particularly strong overall survival data in clinical trials.

Antibody-Drug Conjugates: Precision Medicine in Action

What are they?

Antibody-drug conjugates (ADCs) are a new generation of cancer therapies that combine the targeting power of monoclonal antibodies with the cancer-killing power of chemotherapy—but delivered with precision.

Think of ADCs like a “smart bomb”:

• The antibody seeks out cancer cells with a specific protein.

• Once attached, the chemotherapy payload is delivered directly into the cancer cell, sparing more of the healthy tissue.

  
  

Two groundbreaking ADCs:

• Enhertu (trastuzumab deruxtecan): Targets HER2-low and HER2-positive breast cancers.

• Trodelvy (sacituzumab govitecan): Approved for triple-negative breast cancer (TNBC) and HR+/HER2- MBC that has already been treated with endocrine and chemo therapies.

  
  

Who gets them?

• Enhertu is for people with HER2-positive MBC and more recently for HER2-low breast cancers, which now includes many patients previously considered “HER2-negative.”

• Trodelvy is used in TNBC after two prior therapies or in HR+ MBC after hormone and chemo treatment.

  
  

What to expect:

These drugs are given by IV infusion every few weeks. Your team will monitor your blood counts, heart function, and watch for any lung-related symptoms (especially with Enhertu).

Common side effects:

• Nausea

• Hair loss

• Fatigue

• Diarrhea

• Neutropenia (low white blood cells)

Enhertu also carries a risk of interstitial lung disease (ILD), so early detection of coughing, shortness of breath, or chest tightness is important.

Why they matter:

ADCs represent precision-targeted therapy that gives more treatment options for people whose tumors don’t respond well to traditional chemo. Enhertu, in particular, has transformed care for the newly defined category of HER2-low breast cancer—a group that includes nearly 50% of patients with MBC.

Immunotherapy: Boosting Your Body’s Defense Against TNBC

What is it?

Unlike chemo or targeted drugs that attack the cancer directly, immunotherapy helps your own immune system recognize and attack cancer cells.

In breast cancer, immunotherapy has shown the most promise in triple-negative breast cancer (TNBC), which tends to be more aggressive and harder to treat.

Key immunotherapy:

• Keytruda (pembrolizumab): A PD-1 checkpoint inhibitor that works by removing the "brakes" from immune cells, allowing them to detect and fight cancer.

  
  

Who gets it?

Keytruda is used in TNBC that is PD-L1 positive, a marker found via biopsy or molecular testing.

It is often given in combination with chemotherapy as a first-line treatment for metastatic TNBC.

What to expect:

Immunotherapy is usually given as an IV infusion every 3 or 6 weeks, often alongside chemo.

Common side effects:

• Fatigue

• Rash

• Nausea

But because immunotherapy revs up the immune system, it can also lead to immune-related side effects like:

• Inflammation in the lungs (pneumonitis)

• Colitis

• Thyroid issues

Your team will monitor you closely and may use steroids to manage side effects.

Why it matters:

Immunotherapy has extended survival in some TNBC patients and offers a much-needed option for a group that previously had few targeted therapies.

PARP Inhibitors: Targeting BRCA-Mutated Cancers

What are they?

PARP inhibitors work by exploiting a weakness in cancer cells with BRCA mutations—a kind of inherited mutation that affects the way cells repair DNA damage.

In BRCA-mutated cancer cells, the DNA repair machinery is already compromised. PARP inhibitors make it even harder for these cells to fix themselves, leading to cancer cell death while sparing normal cells.

Common PARP inhibitors:

• Olaparib (Lynparza)

• Talazoparib (Talzenna)

  
  

Who gets them?

These are used in people with HER2-negative metastatic breast cancer who also have an inherited BRCA1 or BRCA2 mutation.

If you haven’t already had genetic testing, talk to your oncologist. Finding a BRCA mutation can open the door to these treatments and inform family risk.

What to expect:

PARP inhibitors are oral pills, typically taken once or twice a day.

Common side effects:

• Fatigue

• Nausea

• Anemia

• Low platelet or white blood cell counts

Routine blood work helps monitor for side effects.

Why they matter:

These drugs offer a targeted alternative to chemotherapy and have been shown to improve progression-free survival in people with BRCA-associated MBC. For many, they’re also better tolerated than traditional chemotherapy.

Bringing It All Together

Navigating metastatic breast cancer is complex, but you don’t have to do it alone—and you don’t have to understand it all at once. What matters most is that you begin to learn about your options and feel empowered to ask questions.

Here’s a quick snapshot of when these treatments are used: