Targeted Therapies for Stages I, II, and III Breast Cancer
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Targeted Therapies for Stages I, II, and III Breast Cancer

What is targeted therapy? What targeted therapies are used for Stages I, II, and III invasive breast cancer? Read on to learn about targeted therapies for invasive breast cancer.

Currently, there are two targeted therapies used for Stages I (one), II (two), and III (three) invasive breast cancer, trastuzumab and pertuzumab. Targeted therapy is used in people who are human epidermal growth factor receptor-2 (HER2)-positive and are receiving, or will receive, chemotherapy. If someone is not going to receive chemotherapy, targeted therapy is not given.

This article will provide you an overview on targeted therapy for invasive breast cancer. You will learn about when targeted therapy is used, how it is given, and what side effects to expect. Keep in mind that the drug therapies mentioned in this article apply to those with invasive breast cancer, Stages I, II, and III. There are many more targeted therapies that are used in metastatic, or advanced breast cancer, but these will not be discussed in this article.

A Brief Overview of Targeted Therapy

Before we go into detail about the drugs used for targeted therapy, let’s discuss some important background information on targeted therapy. 

To begin, targeted therapy is a type of cancer treatment that uses drugs to target proteins involved in the growth and spread of cancer. These treatments mainly target cancer cells which limits damage to healthy cells.

In breast cancer, about 1 in 5 people have tumors that exhibit overexpression of HER2, a receptor on the surface of breast cancer cells. Targeted therapy against the HER2 receptor has been shown to help improve outcomes when used with chemotherapy. It is important to know that only people whose tumors have the HER2 receptor are candidates for HER2-targeted therapies. On the other hand, people whose tumors do not test positive for HER2 are not candidates for HER2-targeted therapies. As a side note, there is an exception where other targeted therapies can be used in advanced breast cancer even in people whose tumors test negative for HER2.

Benefits of Targeted Therapies

 There are benefits for targeted therapies:

  • Targeted therapies are directed against a specific molecule on the cancer cell and are highly effective. 
  • Overall side effects are less severe than with chemotherapy.

Disadvantages of Targeted Therapies

There are drawbacks for targeted therapies as well. Some disadvantages include the fact that

  • Over time, cancer cells can become resistant to targeted therapy. However, resistance can be lowered when targeted therapy is used along with other cancer treatments.
  • Not everyone may be a candidate for targeted therapy. Targeted therapies are only offered if you have the specific drug target on your cancer.

Trastuzumab

Now that we have discussed targeted therapies and how they work, let’s discuss the two targeted therapies that are available for invasive breast cancer. 

First up is trastuzumab. Trastuzumab is given to people who have HER2-positive breast cancer, HER2-positive metastatic breast cancer, and HER2-positive metastatic gastric cancer. This drug is an antibody that acts against the HER2 receptor to inhibit the growth of cancer cells.

For stages I, II, and III breast cancer, trastuzumab is used along with chemotherapy. It is given as an intravenous (IV) infusion every 1 or 3 weeks at a treatment center. Treatment lasts for one year.  Side effects to watch out for are headache, diarrhea, nausea, and chills. Serious reactions occur more often when people are getting their first trastuzumab treatment and are still in the treatment center.

Trastuzumab leads to improved survival compared to chemotherapy alone. In multiple studies with thousands of participants, people who received chemotherapy with trastuzumab for one year had significantly improved disease-free survival compared to people who were given only chemotherapy. In other words, when trastuzumab was added with chemotherapy, the chance of survival was improved.

Another benefit of trastuzumab is that it is widely used and the effects are well known. However despite the benefits, trastuzumab may also cause the following:

  • Infusion reactions: Infusion reactions may occur when the drug is given intravenously. The infusion reaction is characterized by fever and chills and may also include nausea, vomiting, headache, dizziness, and rash. Symptoms usually occur during the infusion. You will be given medications before the infusion to decrease the chance that you will have a reaction. Other times, interrupting the infusion or slowing how fast the infusion is given also helps to manage an infusion reaction.
  • Heart damage: Heart damage (also called cardiomyopathy) occurs in some people. Trastuzumab may cause damage to the heart muscles that results in heart failure. People who have the greatest risk of developing cardiomyopathy are those who are also taking anthracyclines (a type of chemotherapy). Damage to the heart is usually reversible. If you are getting trastuzumab, your heart function will be checked several times throughout treatment. If your heart function gets worse, treatment will be stopped. 
  • Lung damage (also called pulmonary toxicity): Trastuzumab may cause serious lung problems and shortness of breath, particularly if you already have lung disease.
  • Harm to a developing fetus: Getting trastuzumab during pregnancy can cause harm to the fetus. If you have ovaries and are able to get pregnant, you will need to use contraception during treatment and for seven months after treatment. 

Pertuzumab

The second targeted therapy that is available for invasive breast cancer is pertuzumab.

Pertuzumab is approved for HER2-positive breast cancer in combination with trastuzumab and chemotherapy. Like trastuzumab, it is also an antibody drug that acts against the HER2 receptor to inhibit the growth of cancer cells.

For treatment of HER2-positive breast cancer, pertuzumab is used in combination with trastuzumab and chemotherapy. The combination of two targeted therapies and chemotherapy to treat breast cancer can result in more severe side effects, especially diarrhea. 

Pertuzumab is given as an intravenous (IV) infusion every three weeks for up to one year. Infusions are given at a treatment center. Possible side effects include diarrhea, anemia, abdominal pain, hair loss, low white blood cell count (neutropenia), nausea, fatigue, rash, numbness, tingling, and burning in the hands and feet. Some people cannot receive a whole year because of severe diarrhea.

You may be wondering if there is a reason to add pertuzumab to your treatment. Evidence shows that adding pertuzumab along with trastuzumab and chemotherapy can reduce the risk of breast cancer coming back in other parts in the body. The benefits of pertuzumab outweigh the downsides If your lymph nodes had cancer in them.

The serious problems of pertuzumab include

  • Heart problems, specifically with the pump function of the heart. Sometimes pertuzumab can cause the left side of the heart to stop pumping as well as it should. 
  • Harm to a developing fetus: Exposure to pertuzumab during pregnancy can result in fetal harm. If you have ovaries and can become pregnant, use contraception during treatment and for seven months after treatment.

Pertuzumab may also cause reactions during the time you are being given the medicine. Reactions include fever, chills, fatigue, and headache during or after an infusion. 

If you are getting pertuzumab, you will be monitored for infusion reactions during and after each infusion. If an infusion-related reaction occurs, then your nurse will slow or interrupt the infusion and give you other medicines.

Summary Table

A summary table of the targeted therapies used for invasive breast cancer is below. Trastuzumab and pertuzumab are similar in several ways, but pertuzumab is used when there is lymph node involvement.

DRUG NAMEAPPROVED INHOW USEDHOW GIVENTREATMENT DURATION
Trastuzumab(Brand name Herceptin®)Treatment of stages I, II, and III  HER2-positive breast cancerTreatment of HER2-positive metastatic (advanced) breast cancerHER2-positive metastatic gastric cancerIn combination with chemotherapyIntravenous infusion1 year
Pertuzumab(Brand name Perjeta®)Treatment of lymph node-positive  HER2-positive breast cancerHER2-positive metastatic (advanced) breast cancerIn combination with trastuzumab and chemotherapy when there is lymph node involvementIntravenous infusion 1 year

Can I Skip Targeted Therapy?

Finally, a big question that may come to mind is if targeted therapy can be skipped. If the tumor size is less than 1 cm and there is no lymph node involvement (N0) or only a very small amount of cancer in the lymph nodes (microinvasion, N1mi), skipping targeted therapy may be considered. 

Targeted therapy may not be part of your treatment plan if your pathology report from your surgery shows that you have a low risk of recurrence. An advantage of skipping targeted therapy is that you can avoid all the side effects related to targeted therapy. However, a disadvantage is that there may be a higher risk of recurrence. There is also the possibility that the pathology report missed some cancer cells that could be treated successfully with targeted therapy.


References

  1.  NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Version 2.2019
  2. Cameron, D., Piccart-Gebhart, M. J., Gelber, R. D., Procter, M., Goldhirsch, A., Azambuja, E. D., . . . Jackisch, C. (2017). 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: Final analysis of the HERceptin Adjuvant (HERA) trial. The Lancet,389(10075), 1195-1205. doi:10.1016/s0140-6736(16)32616-2
  3. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. (2017). New England Journal of Medicine,377(7), 702-702. doi:10.1056/nejmx170011
  4. Herceptin (trastuzumab) [prescribing information]. San Francisco, CA: Genentech, Inc.; November 2018.
  5. Perjeta (pertuzumab) [prescribing information]. San Francisco, CA; Genentech, Inc.; January 2020.