Answer to Question #152110 in Molecular Biology for Elena

Question

A 45 year-old woman complaining of breast pain was diagnosed with having HER2-positive breast cancer. The patient underwent lumpectomy followed by a period of chemotherapy including adjuvant treatment. Over the course of their treatment, the patient developed a urinary tract infection that required antimicrobial therapy, which initially consisted of a trimethoprim/sulfametoxazole combination drug. However, the patient during the course of her therapy suffered multiple recurrent infections and was, consequently, enrolled in a clinical trial to test the efficacy of a new mannoside anti-infective agent. Question: Discuss the mechanisms underpinning current therapeutic strategies for treating HER2-positive breast cancer. In your discussion, you should include details about managing therapeutic resistance and adverse side effects such as cardiotoxicity.

Answer 1

ANSWER

The HER2 positive gene creates HER2 proteins or receptors. Overexpression of HER2 protein causes abnormal reproduction of breast cells. Along with tumor grade and cancer stage, HR and HER2 status help determine options.

Chemotherapy might be done before surgery to shrink the tumor, after surgery to kill the remaining cancer cells, as a treatment for cancer that has spread or combined with other medications.

Radiation can be carried out after surgery to lower the chances that cancer can return or if one's cancer has spread to other body parts. External beam radiation is carried out using a machine that directs radiation to the area where the cancer was. In brachytherapy, doctors put radioactive pellets inside one's body for short periods of time.

Surgical operations are done for cancer stages one through three. In lumpectomy or breast-conserving surgery, the surgeon removes the tumor and some surrounding tissue. In a mastectomy, the entire breast is removed. There is also sentinel lymph node biopsy(SLNB) where the surgeon removes only the lymph node(s) under the arm to which cancer would likely spread first. In axillary lymph node dissection(ALND), the surgeon removes many(usually less than 20) lymph nodes from under the arm.

When it comes to targeted therapy, doctors normally start HER2 treatment with special drugs, targeted therapies. They block HER2 receptors to help keep one's cancer cells from growing.

If one's HER2 positive breast cancer is hormone receptor-positive, then one may also take drugs that stop the hormone estrogen from attaching to the cancer cells.

 Shortcomings are resulting from these therapeutic mechanisms for HER2 positive breast cancer. In chemotherapy, chemo drugs kill fast-growing cells. But because these drugs travel throughout the body, they can affect normal, healthy cells that are fast-growing too. Doctors try to give chemo at levels high enough to treat cancer while keeping side effects at a minimum. They also try to avoid using multiple drugs that have similar side effects. The most common medications used for cardiotoxicity treatment include: Beta-blockers, which slow down a patient's blood pressure and strengthen the heart muscle can reduce palpitations and arrhythmias, hypertension, and heart failure.

Before undertaking any therapeutic medication, one should inform the doctor of their medical history and possible severe allergies.

REFERENCES

Hunter, F. W., Barker, H. R., Lipert, B., Rothé, F., Gebhart, G., Piccart-Gebhart, M. J., ... & Jamieson, S. M. (2020). Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. British journal of cancer, 122(5), 603-612.

de Paula Costa Monteiro, I., Madureira, P., De Vasconcelos, A., Humberto Pozza, D., & Andrade de Mello, R. (2015). Targeting HER family in HER2-positive metastatic breast cancer: potential biomarkers and novel targeted therapies. Pharmacogenomics, 16(3), 257-271.

Riethdorf, S., Müller, V., Zhang, L., Rau, T., Loibl, S., Komor, M., ... & Hilfrich, J. (2010). Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clinical cancer research, 16(9), 2634-2645.