What's Coming Up for Stage II and III Breast Cancer?

Written by Stephanie Watson
Medically Reviewed by Melinda Ratini, MS, DO on September 17, 2025
12 min read

Your breast cancer stage plays an important role in your treatment choices. For stages II and III, treatment often involves some combination of chemotherapy, radiation therapy, surgery, targeted drugs, hormone therapy, and immunotherapy. 

Treatments your doctor recommends also depend on the type of breast cancer you have, such as hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-positive (HER2-positive), or triple-negative breast cancer.

A few medicines are newly approved to treat early-stage breast cancers, and many more are coming down the research pipeline. These promising new therapies might improve survival even more when you're diagnosed with stages II and III breast cancer. 

Some work differently from current treatments. Others have fewer side effects.

"There's a lot of exciting data, new medications, and new therapies — and they apply to different groups of breast cancer patients," says Krushangi Patel, MD, a hematologist-oncologist at City of Hope Orange County in Long Beach, CA.

Therapies listed below are recently approved or in clinical trials. Researchers are still looking at how each one works and the side effects it might cause. Some could come to market in a few months or years. Others might never get approved. 

More breast cancer treatments, which aren't included here, are in earlier stages of development.

Both Kisqali and Verzenio are targeted therapies known as CDK4/6 inhibitors. They've been approved for a few years to treat some early-stage breast cancers. They're also approved for late-stage breast cancer. What's new is the finding that when added to hormone therapy, each of these medicines can lower the risk of a recurrence, which is the chance of the cancer coming back after treatment.

What do Kisqali and Verzenio do?

CDK4/6 are proteins that control how quickly cells grow and divide. In some people with breast cancer, these proteins are overactive, and they make cancer cells grow out of control. CDK4/6 inhibitors block these proteins to slow the growth of cancer cells. 

How are Kisqali and Verzenio different from other breast cancer treatments?

Instead of killing all of the cancer cells in their path, like chemotherapy and radiation do, Kisqali and Verzenio target very specific proteins that are involved in cell division. For that reason, they're less likely to damage healthy cells.

How are Kisqali and Verzenio taken?

Kisqali and Verzenio are pills that you take with a hormone therapy such as fulvestrant (Faslodex), tamoxifen, or an aromatase inhibitor. Hormone therapy stops your body from making estrogen, which helps breast cancer grow. For early-stage breast cancer, you take Kisqali once a day for 21 days. Then you stop the medicine for seven days. Verzenio is taken twice a day.

Who benefits from Kisqali and Verzenio?

These medicines are for people with HR-positive, HER2-negative stage II and III breast cancer who are at high risk for a recurrence.

Where are Kisqali and Verzenio in the research pipeline?

In 2024, the FDA approved Kisqali to lower the risk of recurrence in early-stage breast cancer. Verzenio has been approved for early-stage breast cancer since 2021. Both drugs are also approved to treat late-stage breast cancer.

Kisqali and Verzenio study results

Researchers reviewed four studies on CDK4/6 inhibitors plus hormone therapy in people with early-stage HR-positive, HER2-negative breast cancer. People who took these medicines were much more likely to be still alive and cancer-free for three to four years later than people who didn't take them. The study authors said the improved survival from CDK4/6 inhibitors is partly due to a reduced risk of recurrence.

What's next?

These medicines are already approved. In future studies, researchers will try to learn how exactly Kisqali and Verzenio improve survival.

Enhertu is a type of targeted therapy called an antibody-drug conjugate. It delivers chemotherapy straight to the cancer cells.

What does trastuzumab deruxtecan (Enhertu) do?

Trastuzumab is a monoclonal antibody. It targets the HER2 protein on the surface of some breast cancer cells. Once it attaches to the HER2 protein, it releases the chemotherapy drug deruxtecan to kill the cancer.

How is trastuzumab deruxtecan (Enhertu) different from other breast cancer treatments?

This medicine is more precise than chemotherapy. Instead of randomly killing breast cancer cells, it targets cancer cells that have the HER2 protein.

How is trastuzumab deruxtecan (Enhertu) taken?

Enhertu comes as an infusion that you get through an IV. For breast cancer, it's given once every three weeks until the cancer starts to grow or the side effects are too much to tolerate.

Who benefits from trastuzumab deruxtecan (Enhertu)?

Enhertu is approved for some people with late-stage HER2-positive, HER2-low (meaning low levels of this protein), and HR-positive breast cancers. Some doctors also use it as salvage therapy for stage II and III breast cancers. Salvage therapy is a medicine you take after other treatments haven't worked. "It's very exciting because it means that we have a way to prevent these patients from getting recurrence, which was one of the big challenges with HER2-positive breast cancers," Patel says.

Where is trastuzumab deruxtecan (Enhertu) in the research pipeline?

Enhertu is already approved for HER2-positive, HER2-low, and HR-positive breast cancers that are advanced or can't be removed surgically. It's in phase III trials for early-stage HER2-positive breast cancer.

Trastuzumab deruxtecan (Enhertu) study results

DESTINY-Breast11 is a phase III study that looked at the effects of Enhertu before surgery in people with early-stage HER2-positive breast cancer. One group got Enhertu, followed by the chemotherapy drug paclitaxel (Taxol) and two HER2-targeting drugs — pertuzumab (Perjeta) and trastuzumab (Herceptin). The other group took two chemotherapy drugs, followed by Herceptin and Perjeta. More people in the Enhertu group had no signs of cancer in breast tissue and lymph nodes that were removed during surgery than in the other group.

What's next?

Researchers will want to learn whether Enhertu also improves survival in early-stage breast cancer. "It's probably [going to be] the next drug to leap into management of stage II and III," says Hal Burstein, MD, PhD, a medical oncologist at Dana-Farber Cancer Institute in Boston, MA.

This treatment combines two targeted medicines with one hormone therapy drug. It's for people who have a mutation called PIK3CA in their cancer cells that makes it easier for the cancer cells to grow. 

What do Itovebi, Faslodex, and Ibrance do?

These three medicines attack cancer in different ways. Itovebi is a PI3K inhibitor. It blocks a pathway that helps cancer cells grow. Faslodex is a type of hormone therapy called a selective estrogen receptor degrader (SERD). It stops estrogen from getting into cancer cells and helping them multiply. Ibrance is a CDK4/6 inhibitor. It blocks CDK4/6 proteins that are overactive in breast cancer cells.

How are Itovebi, Faslodex, and Ibrance different from other breast cancer treatments?

Faslodex plus Ibrance are already part of the standard treatment for HR-positive metastatic breast cancer. Adding Itovebi may help improve survival in people with a PIK3CA mutation.

How are Itovebi, Faslodex, and Ibrance taken?

Itovebi and Ibrance are tablets you take once a day. Faslodex is an injection given three times in the first month and then once a month.

Who benefits from Itovebi, Faslodex, and Ibrance?

This three-drug combination is for people with HR-positive, HER2-negative metastatic or locally advanced breast cancer with a PIK3CA mutation.

Where is Itovebi, Faslodex, and Ibrance in the research pipeline?

The drug combination is FDA-approved for people with HR-positive, HER2-negative metastatic breast cancer and a PIK3CA mutation. It still needs to be studied in early-stage breast cancers.

Itovebi, Faslodex, and Ibrance study results

A phase III study called INAVO120 looked at the effects of adding Itovebi to Faslodex and Ibrance in people with HR-positive, HER2-negative metastatic breast cancer and a PIK3CA mutation. People who also got Itovebi lived longer without their cancer growing than those who just got Faslodex and Ibrance. 

What's next?

Adding Itovebi to Faslodex and Ibrance is only approved for certain late-stage breast cancers, but that might change in the future. Itovebi is being studied in earlier-stage breast cancers. "The hope is that, in the future, we can use tumor molecular testing to look for PIK3CA mutations. And then, if appropriate, begin to add that drug to improve long-term outcomes," Burstein says.

Trodelvy is an antibody-drug conjugate. It combines the monoclonal antibody sacituzumab govitecan with the chemotherapy drug SN-38. 

Keytruda is a type of immunotherapy drug called a checkpoint inhibitor. Checkpoints are proteins that help your immune system tell which cells are your own and which are dangerous. Cancer cells sometimes use checkpoints to hide from the immune system. 

What does Trodelvy plus Keytruda do?

The antibody part of Trodelvy finds cancer cells that have the protein Trop-2 on their surface and attaches to them. Then, it releases the chemotherapy drug into the cells. Keytruda helps your immune system find and attack cancer cells. 

How is Trodelvy plus Keytruda different from other breast cancer treatments?

Adding an antibody-drug conjugate to immunotherapy may attack the cancer more effectively and improve survival compared to current treatments. 

How is Trodelvy plus Keytruda taken?

Trodelvy comes as an infusion once a week. Keytruda is an injection given once every three to six weeks.

Who benefits from Trodelvy plus Keytruda?

Trodelvy is approved for people with late-stage triple-negative breast cancer. Keytruda is approved for both early- and late-stage triple-negative breast cancer. 

Where is Trodelvy plus Keytruda in the research pipeline?

The combination of the two drugs is showing promise for both advanced and early-stage triple-negative breast cancers.

Trodelvy plus Keytruda study results

The phase II NeoSTAR study included 50 people with early-stage triple-negative breast cancer who had not received any treatment. After taking Trodelvy plus Keytruda, 32% of participants had no sign of cancer in the tissue removed during surgery.

What's next?

More research is needed to learn how long people need to take these medicines to have the best response. Another question being investigated is whether Trodelvy plus Keytruda is enough to control the cancer or if these medicines need to be combined with chemotherapy for better results. Clinical trials are also looking at adding Trodelvy for people who still have cancer after chemotherapy, Keytruda, and surgery.

Dato DXd is another antibody-drug conjugate. It combines the monoclonal antibody datopotamab with the chemotherapy drug DXd.

What does Dato-DXd do?

Datopotamab finds and attaches to the Trop-2 protein on the surface of breast cancer cells. Then it releases DXd chemotherapy into the cells.

How is Dato-DXd different from other breast cancer treatments?

Dato-DXd is similar to other antibody-drug conjugates for breast cancer. But it includes a different type of antibody and chemotherapy drug compared to other medicines of its kind.

How is Dato-DXd taken?

Dato-DXd comes as an infusion through an IV once every three weeks.

Who benefits from Dato-DXd?

This treatment is for people with HR-positive, HER2-negative breast cancer that is late-stage or that can't be removed with surgery.

Where is Dato-DXd in the research pipeline?

Dato-DXd is already approved for advanced HR-positive, HER2-negative breast cancer. Researchers are now studying it for early-stage breast cancer.

Dato-DXd study results

The I-SPY2.2 phase II trial gave Dato-DXd to 103 people with stage II and III breast cancer. While the treatment didn't achieve the goal response, it did show promise, especially for a group of people with HER2-negative breast cancer.

What's next?

Researchers are doing early studies giving Dato-DXD to people with breast cancer before surgery. They're also looking at combining it with immunotherapy drugs such as durvalumab (Imfinzi). "The hope is that it could become a more routine part of treatment if it's effective," Burstein says.

Imlunestrant is a selective estrogen receptor degrader (SERD). SERDs are a newer type of hormone therapy for breast cancer.

What does imlunestrant do?

SERDs fill estrogen receptors on the surface of breast cancer cells. By doing this, they block estrogen from attaching to its receptors. "The hope is that you make the tumor, which is driven by estrogen receptor activity, slow down or stop its growth," says Burstein.

How is imlunestrant different from other breast cancer treatments?

SERDs are similar to selective estrogen receptor modulators (SERMs) such as tamoxifen. Both types of medicine block estrogen from attaching to receptors on the cancer cells and helping the cancer grow. 

But SERDs are a little bit different. They also reduce the number of estrogen receptors and stop them from working very well. Two SERDs, Faslodex and Orserdu (elacestrant) are already approved to treat breast cancer. Others, such as camizestrant and giredestrant, are in clinical trials.

How is imlunestrant taken?

You take imlunestrant as a capsule or tablet.

Who benefits from imlunestrant?

People with estrogen receptor (ER)-positive, HER2-negative breast cancer benefit from imlunestrant.

Where is imlunestrant in the research pipeline?

Imlunestrant and other SERDs are in phase III clinical trials for both early-stage and advanced breast cancer. 

Imlunestrant study results

EMBER-2 was a phase I study of imlunestrant for postmenopausal women with untreated ER-positive, HER2-negative breast cancer. Researchers found that a 400 mg dose was effective at targeting the estrogen receptor without causing a lot of side effects.

What's next?

SERDs such as imlunestrant have already been well-studied in people with metastatic breast cancer. "Because they're oral and because they seem to be a little more potent than some other anti-estrogen options, there's a lot of interest in trying to move them to the earlier stage setting," says Burstein.

Alpha-lactalbumin (aLA) is a new kind of breast cancer treatment. It's a vaccine that's designed to stimulate the immune system to attack breast cancer cells.

What does the alpha-lactalbumin vaccine do?

Alpha-lactalbumin (aLA) is a milk protein that some types of breast cancer cells release. Healthy breast cells only release aLA during breastfeeding. The vaccine creates an immune response against any cancer cells that release the aLA protein. "The body recognizes the cancer and may be able to then attack it, which normally does not occur," Patel says.

How is the alpha-lactalbumin vaccine different from other breast cancer treatments?

The alpha-lactalbumin vaccine works in a way that's similar to immunotherapies such as Keytruda, which is already approved for some early-stage breast cancers. "The vaccine will likely create that immune response as well," Patel says. "But it isn't quite there yet."

How is the alpha-lactalbumin vaccine taken?

The vaccine comes as an injection given under the skin.

Who benefits from the alpha-lactalbumin vaccine?

Alpha-lactalbumin is for some people with triple-negative breast cancer.

Where is the alpha-lactalbumin vaccine in the research pipeline?

The vaccine is in phase I trials to study its safety and find the most effective dose for early-stage triple-negative breast cancer.

Alpha-lactalbumin vaccine study results

Early lab studies of the vaccine had promising results. It activated an immune response and slowed tumor growth.

What's next?

Based on early results from phase I studies, researchers plan to launch phase II trials of the vaccine. They still need to learn how to increase the vaccine response, such as by adding other cancer treatments like chemotherapy or radiation.

Lutetium-177 NeoBOMB1 is a type of medicine called a radiopharmaceutical. It's a radioactive medicine that researchers are studying for many types of cancer, including breast cancer.

What does lutetium-177 NeoBOMB1 do?

This treatment contains a protein that targets gastrin-releasing peptide receptors (GRPRs), which some breast cancer cells make too much of. The protein is attached to the radioactive substance, lutetium-177. "The protein binds to the cancer cell, and then the radioactivity zaps the cancer cell from very close up," Burstein says.

How is lutetium-177 NeoBOMB1 different from other breast cancer treatments?

The difference is that this treatment delivers radiation to the cancer cells.

How is lutetium-177 NeoBOMB1 taken?

Lutetium-177 NeoBOMB1 is different from radiation that a machine delivers to your body. "This is something that is infused, just like you would give chemotherapy," Patel says.

Who benefits from lutetium-177 NeoBOMB1?

This treatment is for people with HR-positive, HER2-negative breast cancer that produces too much GRPR.

Where is lutetium-177 NeoBOMB1 in the research pipeline?

A lutetium-177 treatment called Lutathera is already approved for some people with neuroendocrine tumors. The treatment is in phase I and II studies of people with metastatic breast cancer. It's not yet being studied in early-stage cancers.

Lutetium-177 NeoBOMB1 study results

Studies of lutetium-177 NeoBOMB1 in advanced breast cancer are under way.

What's next?

This type of treatment is in development for metastatic breast cancer. "I think it's going to be quite a while til we see it for early-stage II or III breast cancer, but it's a very exciting new class that's being explored," Burstein says.

If you're interested in learning about these or other clinical trials of new breast cancer treatments, start with your cancer center. "The first thing you should do is speak to your oncology team and ask, 'Are there appropriate clinical trials for me?'" Burstein suggests. You can also search clinicaltrials.gov, which includes all of the studies being done across the U.S.