Answer to Question #152109 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 roles of the three components of the patient's treatment for her relapsing UPEC infection. Your discussion should include the pertinent virulence factors that contribute to the establishment of the infection and the initial treatment failure.

Answer 1

ANSWER

HER2-positive breast cancer is breast cancer that tests positive for a protein known as epidermal growth factor receptor 2(HER2). HER2 protein promotes the growth of cancer cells. In about 1 of every 5 breast cancers, the cancer cells have extra copies of the gene that makes the HER2 protein. HER2- positive breast cancers tend to be more aggressive than other types of breast cancer. The HER2 genes create HER2 proteins or receptors. These receptors help control the growth and repair of breast cells. Overexpression of HER2 protein causes out of control reproduction of breast cells.

For a lumpectomy, the surgeon is to remove the tumor and some surrounding tissue. Size, location and the number of tumors help determine the need for breast-conserving surgery and whether to remove the lymph nodes. The stage at diagnosis should be keenly monitored. Lumpectomy can be effective when cancer has not spread outside the breast. Metastatic breast cancer which has spread to distant areas of the body is harder to treat. Cancer can spread from the lymph nodes to distant organs and tissues.

Chemotherapy is a systemic treatment. Powerful drugs can seek out and destroy cancer cells anywhere in the body. During a response to therapy, it can be hard to predict whether a particular therapy will be effective or produce intolerable side effects.

Targeted treatments work to attack a specific type of cancer cell. In the case of HER2-positive breast cancer, these drugs would target cells expressing the HER2 protein.

The development of a urinary tract infection signals that breast cancer had spread to distant areas of the body, making it harder to treat. A UTI develops when microbes such as bacteria enter the urinary tract and cause infection. An antimicrobial therapy kills or inhibits the growth of such bacteria. Trimethoprim is an antibiotic that eliminates bacteria that cause urinary tract infections. It does not work for viral and other protozoan infections.

Sulfamethoxazole and trimethoprim antibiotics are usually combined during medication. This is used to treat a wide variety of bacterial infections including UTI. However, this treatment may develop subsequent side effects such as nausea, vomiting, diarrhea, loss of appetite, and serious muscle weakness.

Mannosides, small molecule drugs that contain a mannose sugar group, may be able to treat and prevent urinary tract infections(UTIs), without inducing antibiotic resistance. However, The bacteria that cause UTIs often develop resistance to antibiotics, making those, medications less effective.

The major factors that could have led to the initial treatment failure include; late stage of HER2 positive patient; the bigger size and more aggressive grade of the primary tumor; infection of the lymph node and distant organs; complicated overall health; intolerant side effects to therapy; and old age.

References

Loibl, S., & Gianni, L. (2017). HER2-positive breast cancer. The Lancet, 389(10087), 2415-2429.

Engel, R. H., & Kaklamani, V. G. (2007). HER2-positive breast cancer. Drugs, 67(9), 1329-1341.

Arteaga, C. L., Sliwkowski, M. X., Osborne, C. K., Perez, E. A., Puglisi, F., & Gianni, L. (2012). Treatment of HER2-positive breast cancer: current status and future perspectives. Nature reviews Clinical oncology, 9(1), 16-32.

Dean-Colomb, W., & Esteva, F. J. (2008). Her2-positive breast cancer: Herceptin and beyond. European Journal of Cancer, 44(18), 2806-2812.

Piccart-Gebhart, M. J., Procter, M., Leyland-Jones, B., Goldhirsch, A., Untch, M., Smith, I., ... & Cameron, D. (2005). Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. New England Journal of Medicine, 353(16), 1659-1672.