Breast Cancer: the Clinician's Involvement

For many women, the fear of breast cancer is always present. If the disease develops, early detection is key to its prognosis. Practitioners must emphasize early risk stratification and screenings to reduce the death toll.

Epidemiology

According to the CDC, breast cancer is the second most common cancer in the United States. In 2014, it was diagnosed 236,968 times, resulting in 41,211 deaths.¹ The CDC also reported that breast cancer is the most common cancer in women and the most common cause of death for Hispanic women.¹ On average, 90% of women survive 5 years, with 83% surviving 10 years._² Table 1 shows how the CDC demonstrates the correlation of increasing age and the percentage of US women who developed breast cancer within 10- to 30-year intervals.¹

Pathology

Breast cancer’s initial location influences treatment and prognosis. Adenocarcinoma encompasses ductal cancers, including ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC). DCIS and LCIS are classified as noninvasive ductal cancers. They are usually classified as early-stage cancers and have high treatment success rates. Results of a 10-year DCIS study showed that the survival rate was 97%, with the risk of death as low as 1.9%.³ Results from another LCIS study showed a mean survival rate of 10.9 years and a mortality rate also low, at 2.9%.3 IDC and ILC occur in the same areas of the breast as DCIS and LCIS but are invasive to the surrounding tissue. IDC and ILC are the most and second most common types of invasive cancer, respectively. IDC and ILC collectively represent 80% of breast cancer cases. Additional types, which are rare, include inflammatory (in 1%-6% of cases), medullary (2%- 3%), mucinous (3%), tubular (1%-2%), cribriform (5%-6%), and papillary breast cancers (1%-2%).⁴

Large-cell neuroendocrine carcinoma is a rare type of breast cancer characterized by its large, pale cells. It typically occurs in older women, is very aggressive, often metastasizes, frequently recurs, and has a poor prognosis. Anthracycline chemotherapy and radiation are often the first-line treatments of this type of cancer (Table 2).⁵

Squamous cell carcinoma is a rare, aggressive form of breast cancer. It is often hormone receptor (HR)-negative, which worsens the patient’s prognosis. Originating in the epithelial cells, which predominantly appear in the skin covering the breast,⁶ this is another form of breast cancer common in older women. After forming from skin cancer, the nipple, or a deep epidermal cyst within the breast, squamous cell cancer travels to the lymph nodes just 10% of the time.⁶ Table 3 shows the different categories of breast cancer and their distinct presentations.^4-6

Although many risk factors for breast cancer are modifiable for the disease, many others are not (table 4).⁷

Screening

Women are encouraged to perform self-exams regularly to assess any changes in the breast or surrounding tissue early. Mammograms remain the standard diagnostic tool, followed by biopsy to confirm the presence of malignancy. The American Cancer Society (ACS), the National Comprehensive Cancer Network, and the US Preventive Services Task Force provide guidelines for the appropriate screening measures and their frequency in relation to a woman’s age (Table 5).^8,9

Testing of the tumor’s hormone status (ie, estrogen receptor [ER] positive/negative and progesterone receptor [PR] positive/ negative) and HER2 protein involvement is important to optimize breast cancer treatment. If the malignant tumor produces an excess of HER2, a drug such as trastuzumab (Herceptin) or ado-trastuzumab emtansine (Kadcyla) may be initiated; their cytotoxic actions can efficiently destroy the cancer cells.¹⁰ Triple-negative breast cancer is characterized by ER-negative, PR-negative, and HER2-negative results, making it unresponsive to typical therapies and resulting in a poorer prognosis. The physical presentation of breast cancer may include a lump or lumps within the breast tissue, a change in size or appearance, changes to the outer skin over the breast, unexplained nipple discharge, a newly inverted nipple, skin changes surrounding the nipple, and redness or pitting of the breast.⁷ Health care professionals must educate women about these clinical presentations and counsel them to seek immediate medical attention if any of these symptoms are observed. Detection of a breast cancer tumor while it is considered small (<2 cm) and categorized as low-grade allows for more successful and less invasive treatment methods.¹¹

Treatment

As with all other cancers, the prognosis is classified in stages ranging from I to IV, depending on location and metastases. Tumors are graded based on histopathology, assessing the nuclear grade, mitotic rate, and cellular differentiation. Each of these 3 categories is graded from 1 to 3, with 1 being the least characteristic and 3 being most.¹¹ The total score from these 3 parameters may range from 3 to 9, with 3 denoting a higher survival probability and less severity than a score of 9.^11,12 Plainly, if a tumor is grade 9, it is fast growing, highly differentiated from normal tissue cells, and rapidly dividing. Table 6 shows common classes of medications used in the adjuvant, neoadjuvant, and prophylactic treatment of breast cancer and their most common adverse effects (AEs).¹⁰ These may be used in combination with surgery, radiation, and chemotherapy.

HER2 is an epidermal growth factor. In excess, it promotes breast cancer cell growth. HER2 receptor blocker medications are specific to HER-positive cancer cells in their cytotoxic effects. The target drugs, specifically trastuzumab, are cardiotoxic, resulting in a high incidence of asymptomatic left ventricular ejection fraction and overt heart failure. These medications require regular echocardiograms and multigated acquisition scans to monitor these AEs. The medications are often used in combination with chemotherapy to maximize benefit.^10,13

Depending on whether the presentation of cancer cells results in either ER- or PR-positive or -negative status, hormone therapy is employed as adjuvant or neoadjuvant therapy, according to the type of management desired. Hormone therapy is achieved by using selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs) or even through surgical removal of the ovaries.

Tamoxifen, a SERM, is specifically known to lower the risk of recurrent breast cancer in patients with hormone-positive DCIS who have taken tamoxifen consistently for 5 years.^10,13 When treatment with a SERM has failed, other medications within this class should be avoided.¹³ Many selective serotonin reuptake inhibitors, including paroxetine, interact with tamoxifen through major cytochrome P450 (CYP) activity. Venlafaxine is commonly used to alleviate menopausal symp- toms caused by SERMs because of its lack of CYP interaction.

AEs of AIs may warrant further screening, such as regular bone-density dual-energy x-ray absorptiometry scans, and prophylactic supplementation with vitamin D and calcium.

When selecting SERM and AI therapies, the patient’s menopausal status and comorbidities (see Figure14) and the AE profile of the selected therapy should be assessed.

In women who have undergone oophorectomy surgery, AIs and SERMs have been used to maximize breast cancer treatment.¹³ According to the ACS, some common adjuvant therapy regimens combine SERM and AI therapies for a prolonged treatment period (see Online Table 7).¹³

Another medication that works similarly to AIs and SERMs is fulvestrant (Faslodex), which targets estrogen receptors for destruction and is exclusive to postmenopausal women.^6,7 This medication is used in advanced treatment after other endocrine therapies have failed.¹³ This medication is available as two 250-mg prefilled syringes. The dose is given as 250-mg/5-mLintramuscular injections, 1 in each buttock, 2 weeks apart, and then monthly afterward.¹³

A newer agent recently approved by the FDA for advanced and metastatic breast cancer is abemaciclib (Verzenio). This medication is reserved for breast cancer that is HR-positive and HER2-negative. It is recommended to be given with fulvestrant and can be used as monotherapy when endocrine therapy or chemotherapy has been used previously. In a clinical trial of 669 patients, when abemaciclib was used in combination with fulvestrant, the median progression-free survival rate was 16.4 months.¹⁵ Similarly, another newer agent, ribociclib (Kisqali), also targets HR-positive/HER2-negative breast cancer. It is reserved for postmenopausal women with advanced-stage or metastatic cancer and is to be used in conjunction with letrozole (Femara).¹⁶ Palbociclib (Ibrance) and everolimus (Afinitor) are 2 target drugs used in combination with AIs to treat advanced- stage breast cancer.¹⁰ Online Table 8 categorizes some important drug interactions of these classes.¹⁷

Prevention

Cancer is still a medical enigma. The medical community continues to struggle with detection and prevention. It is estimated that 5% to 10% of breast cancers can be linked to genes and gene mutations—specifically, the breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2).⁷ Hormone therapy or preventive surgery may be used as breast cancer prophylaxis by women who inherit the BRCA genes and by women who are at particularly high risk of developing breast cancer.⁷ Online Table 9 shows breast cancer preventive therapies.

Comorbidities associated with breast cancer include gastroesophageal reflux disease, anxiety, stress, depression, pain, hypertension, and insomnia.¹⁸ Additionally, breast cancer medications can cause such AEs as cardiovascular events, joint or muscle pain, and osteoporosis.^7,10,18 As the number of medications increases to ameliorate the AEs and manage the disease state, the risk of drug interactions will increase. Health care providers must evaluate the addition of each new medication.

Health Care Professional's Role

Early diagnosis is a key component in treating breast cancer; stressing the importance of annual screenings and checkups is a critical counseling point. Clinician involvement should also encompass professional practitioners outside direct medical involvement, such as social workers and case managers, to include all avenues of disease state management and effectively navigate the patient through the course of treatment. Examples of these are counseling or support groups, financial assistance programs, and medication therapeutic management. A health care professional should help the patient learn about her disease state and its pathology and prognosis.¹³ By employing SERM- approved therapy prophylactically in certain patients, health care professionals could reduce a patient’s risk of developing breast cancer.¹⁹ This directly affects the clinical pharmacist’s role of providing medication therapy management, improving adherence, and monitoring drug interaction.^18,19 Clinician involvement and teamwork are at the epicenter of optimizing and developing better treatment options for the management of breast cancer.

Conclusion

Breast cancer, although a daunting diagnosis, is becoming a more survivable cancer. Many new drug therapies offer hope and promise. Clinicians can promote earlier screenings and risk stratification to expedite BC diagnosis and thus a better prognosis. Breast cancer still plagues many women, but it has the potential to be cured.

Jerry A. Barbee Jr, PharmD, BCPS, CPh, and Glenn Schulman, PharmD, MS, BCPS, BCACP, BCGP, are clinical pharmacists at HCA West Florida Hospital in Pensacola, Florida. Joseph Adelufosi is a PharmD candidate at the University of South Florida in Tampa. Aericka O’Neal-Scott is a PharmD candidate at Florida Agricultural and Mechanical University in Tallahassee.

References

• Breast cancer statistics. CDC website. cdc.gov/cancer/breast/statistics/index.htm. Updated June 7, 2017. Accessed September 3, 2017.
• Breast cancer: statistics. American Society of Clinical Oncology’s cancer.net website. cancer.net/cancer-types/breast-cancer/statistics. Published April 2017. Accessed September 3, 2017.
• Halls S. Moose & Doc breast cancer. Steven Halls, MD’s, Moose & Doc website. breast-cancer.ca/4b-atypical/. Published October 11, 2017. Accessed October 12, 2017.
• Halls S. Breast adenocarcinoma. Steven Halls, MD’s, Moose & Doc website. breast-cancer.ca/adeno-carc/. Published October 11, 2017. Accessed October 12, 2017.
• Halls S. Large cell neuroendocrine carcinoma of the breast. Steven Halls, MD’s, Moose & Doc website. breast-cancer.ca/largecellys/. Published October 12, 2017. Accessed October 12, 2017.
• Halls S. Pure squamous cell carcinoma within the breast. Steven Halls, MD’s, Moose & Doc website. breast-cancer.ca/squam-carc/. Published October 12, 2017. Accessed October 12, 2017.
• Breast cancer: symptoms and causes. Mayo Clinic website. mayoclinic.org/diseases-conditions/breast-cancer/symptoms-causes/dxc-20207918. Published August 16, 2016. Accessed September 3, 2017.
• American Cancer Society Recommendations for the Early Detection of Breast Cancer. Cancerorg. 2017. Available at: https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.html. Accessed September 3, 2017.
• Breast Cancer Screening Recommendations for Women at Average Risk | Susan G. Komen®. Ww5komenorg. 2017. Available at: http://ww5.komen.org/BreastCancer/BreastCancerScreeningforWomenatAverageRisk.html#Mammography-for-women-ages-40-49. Accessed September 25, 2017.
• Breast cancer: diagnosis. Mayo Clinic website. mayoclinic.org/diseases-conditions/breast-cancer/diagnosis-treatment/treatment/txc-20207949. Published August 16, 2016. Accessed September 3, 2017.
• Halls S. Survival of breast cancer based on stage. Steven Halls, MD’s, Moose & Doc website. breast-cancer.ca/chance-cure/. Published October 11, 2017. Accessed October 12, 2017.
• Guthrie EW. The breast cancer pathology report: what pharmacists need to know. U.S. Pharmacist website. uspharmacist.com/article/the-breast-cancer-pathology-report-what-pharmacists-need-to-know. Published May 19, 2009. Accessed September 3, 2017.
• Hormone therapy for breast cancer. American Cancer Society website. cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html. Updated September 26, 2017. Accessed October 12, 2017.
• Reimers L, Crew KD. Tamoxifen vs Raloxifene vs Exemestane for Chemoprevention. Current breast cancer reports. 2012;4(3):207-215. doi:10.1007/s12609-012-0082-8. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744245/. Accessed October 11, 2017.
• Barrett J. FDA approves drug for certain advanced or metastatic breast cancers. Pharmacy Times^® website. pharmacytimes.com/product-news/fda-approves-drug-for-certain-advanced-or-metastatic-breast-cancers. Published September 28, 2017. Accessed September 29, 2017.
• Simon S. FDA approves Kisqali (ribociclib) for breast cancer. American Cancer Society website. cancer.org/latest-news/fda-approves-kisqali-ribociclib-for-breast-cancer.html. Published March 14, 2017. Accessed September 29, 2017
• Shapiro, Karen, Sherry A. Brown, Stephanie D. Garrett, and Amine Ale-Ali. Rxprep Course Book., 2015. Print.
• Socha T. The role of the pharmacist in treating the cancer patient. Managed Health Care Connect website. managedhealthcareconnect.com/articles/role-pharmacist-treating-cancer-patient. Published November 26, 2012. Accessed September 3, 2017.
• Nguyen N. Contribution to breast cancer prevention for women: a challenge for pharmacists. U.S. Pharmacist website. uspharmacist.com/article/contribution-to-breast-cancer-prevention-for-women-a-challenge-for-pharmacists. Published September 17, 2014. Accessed September 3, 2017.