A program of the UAMS College of Pharmacy For Breast Cancer A program of the UAMS College of Pharmacy Welcome to our Continuing Education program "Prescription for Breast Cancer" funded by an education grant from the Susan G. Komen Foundation for Breast Cancer Research. Funded through unrestricted educational grants by Susan G. Komen Breast Cancer Foundation Arkansas Affiliate

Overview of Breast Cancer Jan K. Hastings, Pharm.D. To begin the overview of breast cancer I’d like to present you with some statistics, which unfortunately are still quite grim despite advances in diagnosis and treatment of breast cancer.

Breast Cancer The most common form of cancer among women The second most common cause of cancer related mortality 1 of 8 women (12.2%) One third of women with breast cancer die from breast cancer Breast cancer is the most common form of cancer in females It is the second most common cause of cancer related mortality. It is second only to lung cancer. The lifetime risk of breast cancer is 1 in 8 women or 12.2% Of those diagnosed with the disease, one-third will die from the disease.

Risk Factors for Breast Cancer Female (1% male) Aging Relative (mother or sister) Menstrual history early on set late menopause Child birth After the age of 30 The 2 strongest risk factors for developing breast cancer include being female (only 1% of cases are diagnosed in males) and also increasing age. Women who have a first-degree relative (a mother or sister) who have developed breast cancer are at an increased risk themselves of developing the disease. The degree of this risk is affected by the age of her relative at diagnosis. If the relative was pre-menopausal at the time of diagnosis, then her own risk is greatest. The risk of breast cancer also corresponds to exposure to both endogenous and exogenous estrogen. The longer the menstrual history the greater the risk. Both early menarche and late menopause are associated with an increased risk of breast cancer. Females who begin menstruation at the age of 12 or younger are at greater risk than those who begin after the age of 14. The risk for women who undergo menopause prior to the age of 45 is about half that of women who undergo menopause after the age off 55. Pregnancy has alternating impacts on the risk of breast cancer. During pregnancy, women are at a higher risk of developing breast cancer. However, once the pregnancy is complete, the risk of breast cancer goes down. Women who have their first child after the age of 30 have a greater risk of breast cancer than those who have children at a younger age.

Exogenous Estrogen Hormonal replacement therapy(HRT) 30% increased risk with long term use Oral Contraceptives(OC) risk slight risk returns to normal once the use of OC’s has been discontinued There is an increased risk of breast cancer associated with the use of exogenous estrogen, such as in hormone replacement therapy (HRT). Women taking long-term estrogens have a 30% increase in the risk of breast cancer, despite the cardiovascular benefits associated with this therapy. The combined use of progestational agents with estrogen does not decrease the risk of breast cancer, as they do with endometrial cancer. In fact, progestational agents may increase the risk of breast cancer. The risk of using HRT in women at risk for breast cancer has become a major debate. There are ongoing studies attempting to weigh the risk/benefit ratio of HRT in women with a prior history of breast cancer. Currently the long-term use of HRT in women with a prior history of breast cancer is not recommended. There has been an increased risk of breast cancer found in women currently taking oral contraceptives. This risk appears to be with long-term use, and returns to normal when the oral contraceptives are stopped.

Risk Factors for Breast Cancer Radiation exposure Breast disease Atpyical Hyperplasia Intraductal carcinoma in situ Intralobular carcinoma in situ Obesity Diet Fat Alcohol Radiation exposure has also been associated with the development of breast cancer. Many women decline to obtain a mammogram due to misconceptions about the risk of radiation exposure during mammography. However, radiation exposure with mammography is negligible. An no studies have shown an increased risk of breast cancer just from the amount of radiation used in mammography. Women with atypical hyperplasia of the breast, a proliferative benign breast disease, are at an increased risk of breast cancer. Intraductal and Intralobular carcinoma in situ or primary breast tumors that are at the time confined to the breast are considered risk factors for invasive breast cancer. Intraductal carcinoma in situ is often treated with breast conserving surgery and radiation. For those patients who are treated this way, the risk of the cancer coming back as an invasive cancer is 5 to 10 %. For intralobular carcinoma in situ, it is very common for these patients to simply be watched carefully, rather that treated. For these patients, there is a 25% chance of developing an invasive cancer in either breast within 25 years. Obesity The evidence of an environmental or dietary effect on breast cancer is supported by observations in Japanese American women. The risk of breast cancer is lower in Japan. However, the risk of breast cancer in Japanese women who move to the US approaches that of women born in the US. This was once proposed to be due to the increased fat content of the American diet. However, this has not shown to be true with groups eating low fat diets. Currently, there is no clear link between dietary fat and breast cancer. There is a slight increased risk of breast cancer associated with alcohol intake.

Genetics BRCA-1 BRCA-2 P53, Rb-1 Her-2/neu, c-erB2, c-myc Breast cancer has been linked to mutations in specific genes. Familial breast cancers or breast cancers that seem to run in families have been linked to mutations in the BRCA-1 gene. In non-familial breast cancer, or sporadic cases, they rarely find mutations in BRCA-1. BRCA-1 mutations have also been linked to ovarian cancer. Mutations in BRCA-2 have been linked to both male and female familial breast cancers- but not ovarian cancer. P53 and Rb-1 are tumor suppressor genes. Mutations in these have also been linked to breast cancer. C-erB2, Her-2/neu, and c-myc are oncogenes. Amplifications and mutations in these oncogenes have also been linked to breast cancer. Women with mutations in P53 and BRCA-1 have a lifetime risk of breast cancer of 85%.

Staging of Breast Cancer The American Joint Committee on Cancer (AJCC) has designated staging by TNM T= tumor size N = lymph node involvement M = metastasis The American Joint Committee on Cancer (AJCC) has designated staging by stages 1 through 4. The primary differences between the stages is based on tumor size, the degree of lymph node involvement, the presence of inflammatory signs, and evidence of metastasis. Breast cancer primarily metastasizes to the bone, lung, liver, and brain. Tumor size is a strong predictor of outcome. The risk of relapse also corresponds to tumor size. The presence and number of axillary lymph nodes involved is also predictive of survival

Stage 1 Tumor < 2.0 cm in greatest dimension No nodal involvement (N0) No metastases (M0) Stage 1 breast cancer involves primarily small tumors (less than or equal to 2 cm) with no known lymph node involvement and no metastases to other organs. About 40 to 50% or women present at this stage. 30% will relapse following local regional treatment.

Stage II Tumor > 2.0 < 5 cm or Ipsilateral axillary lymph node (N1) No Metastasis (M0) In general, stage 2 breast cancers are characterized by either slightly larger primary tumor than stage 1 (between 2 and 5 cm) or if there is lymph node involvement. About 70% of stage II patients will relapse following treatment.

Stage III Tumor > 5 cm (T3) or ipsilateral axillary lymph nodes fixed to each other or other structures (N2) involvement of ipsilateral internal mammary nodes (N3) Inflammatory carcinoma (T4d) In general, stage III consists of large tumors (greater than 5 cm) with signs of inflammatory breast cancer. Also if ipsilateral nodes are involved where the tumor has caused the node to be fixed to another node or to other structures it is designated stage 3. Also metastasis to ipsilateral internal mammary lymph nodes gets a designation of stage 3.

Stage IV (Metastatic breast cancer) Any T Any N Metastasis (M1) Stage 4 means any metastatic breast cancer no matter what size the tumor or if there is nodal involvement or not. If it is metastatic, it is stage 4. In general, stage 4 is not considered curable. The goals are to increase the quality of life and extend survival time.

Types of breast cancer In situ Invasive Intraductal (DCIS) Intralobular (LCIS) Invasive Infiltrating ductal carcinoma Tubular carcinoma Medullary carcinoma Mucinous carcinoma There are 2 primary classifications of in situ breast cancer. These are ductal carcinoma in situ and lobular carcinoma in situ. Ductal carcinoma or non-infiltrating or intraductal carcinoma is malignant epithelial cells confined to the mammary ducts with no evidence of invasion of the basement membranes. In the past, DCIS was treated with mastectomy, which resulted in cure for 98% of patients. Screening programs have increased the diagnosis of DCIS. With more women being diagnosed with DCIS, breast-conserving therapy is more desirable. This has become a most controversial area in the treatment of breast cancer. Lobular ductal carcinoma in situ is not detectable clinically or by mammography. It is considered a risk factor for breast cancer, but not a precursor. The general approach is for careful observation. Bilateral prophylactic mastectomy has been used to treat LDIS. The categories of invasive carcinoma are infiltrating ductal carcinoma (75%), tubular carcinoma, modularly carcinoma, and mucinous carcinoma.

Symptoms and Screening Breast Cancer: Symptoms and Screening

Before getting into symptoms of breast cancer and screening for breast cancer, I think it is appropriate to talk just a little bit about the normal physiology and anatomy of the breast. The breast is a sebaceous gland that is composed primarily of fatty tissue. For purposes of description, the external structure of the breast can be divided into 4 quadrants: the Upper inner quadrant, the lower inner quadrant, the lower outer quadrant and the upper outer quadrant. The upper-outer quadrant of the breast is thicker than the remainder of the breast. This quadrant contains a greater bulk of mammary tissue than the other quadrants and both benign and malignant tumors occur most frequently there. The breast borders are probably more extensive than you realize. The upper border of breast tissue begins at the collarbone. The lower border is at the base of a properly fitted bra. The inner border is the edge of the sternum and the outer border is the anterior axillary line which is the underarm or arm pit. Some women have tails or axillary projections of breast tissue that extend further than the anterior axillary lines into the armpit. It is important this this area be included in the breast self-examination.

The internal structure of the breast is divided into lobes a lot like a grapefruit. Each lobe has a collection of ducts that empty into central ducts. And the central ducts empty into lactiferous or the milk secreting ducts of the nipple. As Sherry discussed, the primary tumor of breast cancers are usually described as lobular or ductal.

Normal breast physiology and anatomy In general breasts should appear symmetrical and balanced. It’s important to note any recent or unusual change in size or shape. Size, of course, varies among women but can vary on the same woman. Slight differences in size and shape between breasts are normal. Size of the breasts can vary with weight and an increase or decrease in fatty tissue can increase or decrease breast size. Breasts may increase in size and be tender during the menstrual cycle due to fluid retention. Breasts may also increase in size during pregnancy and lactation. Breast shape varies with a woman’s age. Ligaments hold the breast to the chest, and as one gets older, the breasts ligaments lose their elasticity and breast sag. The breasts of an aging woman tend to diminish in size as the glandular tissue atrophies and is replace by fat. So the breasts often get flabby and hang lower on the chest. So, as women age, the breast loses its firmness and fullness. It’s very important for a woman to know what kind of changes are normal so she can detect an abnormal change early on. Symmetry and balance Size weight menstrual cycle pregnancy and lactation Texture Shape age

Abnormal signs and symptoms So, lets look at abnormal signs and symptoms. Breast tumors can produce puckering, dimpling, or retractions by disrupting underlying structures. Also, if a tumor is blocking the lymphatic drainage, the pores of the breast skin may become more prominent. This results in an orange peel appearance. In breast self-exam, the nipple should always be squeezed to check for discharge. Any new discharge should be reported to the physician. A milky or clear discharge can be a normal finding in women anytime following childbirth. Greenish discharges are often a sign of mastitis and infection. A bloody discharge is strongly suggestive of breast cancer and should be reported immediately. Any new thickening of the skin or lump or “knot” in the breast should be reported to a physician. It is normal for an adult breast to feel granular, nodular, or lumpy especially premenstrually. However, any new mass or enlargement of an existing mass should be reported to a physician. Breast cancers tend to be hard, with no clear borders and immobile ( attached to skin or underlying structures). A retracted or inverted nipple can be normal and in itself is not a problem. However the recent inversion of a nipple could be a sign of breast cancer. Puckering Dimpling Retraction Nipple discharge Thickening of skin or lump or “knot” Retracted nipple

Abnormal signs and symptoms A recent change in breast size, especially unilaterally can be of concern if not related to a normal physiological change. Breast pain or tenderness during the menstrual period is normal. However, prolonged tenderness may be a sign of breast cancer. It is important to note that most malignant breast lesions are not painful. Inflammatory signs of cancer can be rash or edema. A change in the direction the nipple is pointing may also be a sign of breast cancer. Scaling on nipples can also indicate a problem. Scaling around both nipples could be due to allergy to soap or powder but scaling around one nipple often indicates an abnormality. And then finally a sore on the breast that does not heal should be examined by a physician. Change in breast size Pain or tenderness Redness Change in nipple position Scaling around nipples Sore on breast that does not heal

Methods of Detection Clinical exam by MD or nurse Mammography Monthly breast self-exam (BSE) Methods of Detection There are 3 main screening methods for breast cancer. These are clinical exam by a physician or nurse, mammography, and monthly breast self exam.

Clinical examination Performed by doctor or trained nurse practitioner Annually for women over 40 At least every 3 years for women between 20 and 40 More frequent examination for high risk patients Let’s begin by looking at the clinical exam. Clinical breast exams are recommended annually for women over 40 and at least every 3 years for women between 20 and 40. It should be performed by a physician or a trained nurse practitioner. If the woman has a high risk of breast cancer, her physician may recommend frequent examination. Clinical breast exam has been shown to decrease breast cancer mortality.

Mammography X-ray of the breast Has been shown to save lives in patients 50-69 Data mixed on usefulness for patients 40-49 Normal mammogram does not rule out possibility of cancer completely Mammography is the next method of breast cancer screening. It is an x-ray of the breast but uses the lowest radiation doses. It is the mainstay of breast cancer detection with an 85 to 90% diagnostic accuracy rate which is very high and can detect breast cancers the size of a freckle. However, a normal mammogram does not rule out the possibility of cancer completely. On the other hand, screening mammography has been shown to save lives. This is especially true in women over 50, where routine mammogram leads to a 25 to 30% decrease in breast cancer mortality.

Mammography American Cancer Society recommends: Women (asymptomatic) 40 years of age and older should have a mammogram every year. The American cancer society recommends that asymptomatic women 40 years of age and older should have a mammogram every year.

Mammography-more guidelines Mammogram facility guidelines Avoid mammogram week before period Don’t wear deodorant powder or cream Bring a list of the places and dates of other mammograms,biopsies you’ve had before If you don’t hear from the MD within 10 days, call the facility Some other guidelines to remember about mammogram and to pass on to your patients include making sure the facility is certified by the Food and Drug Administration. It’s best for the patient to use a facility that either specializes in mammography or performs many mammograms a day. If the patient is satisfied with the facility, she should continue to go there on a regular basis so that her mammograms can be compared from year to year. If she changes facilities, she should ask for her old mammograms to take with her to the new facility so they can be compared to the new ones. If the patient has sensitive breasts, she should try having her mammogram at a time of the month when her breasts would be least tender. She should try to avoid the week right before her period. This will help lessen the discomfort. Deodorant powder or cream could interfere with the quality of the mammogram and shouldn’t be worn for the test. When going for a mammogram the patient should take a list of the places and dates of mammograms, biopsies, or other breast treatments that she has had before. And finally, if the patient does not hear from her physician within 10 days, she shouldn’t assume that the mammogram was normal. She should confirm this by calling the physician or the facility.

Free Mammograms Medicare Arkansas Breast Cancer Control Program Breast and Cervical Cancer Control Program of the Arkansas Department of Health Of all Arkansas women between the ages of 45 and 64, 47,000 have no health insurance and thus no coverage for mammograms or other screening procedures. Fortunately, state and federal resources for treatment for uninsured women are on the rise.

Medicare Women over 65 Medicare pays for mammograms for women over 65.

Arkansas Breast Cancer Control Program Started in 1999 Eligibility Women 40 or older No insurance Income at or below 2 times the poverty level Call county or state heath department 1-800-482-5400 The state Breast Cancer control Program created by the Breast Cancer Act of 1997 will offer free screening, diagnostic services and treatment to women who are eligible. Eligible women must be 40 or older, have no insurance and have an income that’s 2 times poverty level. Patient may call local or state health department for more information.

Eligibility for ABCCCP Mammogram 50 years or older and At or below 200 percent poverty OR Between 40 and 49 and A breast cancer survivor or have a mother, daughter, or sister who has breast cancer and The state Breast Cancer and Cervical Control Program of the Arkansas Department of Health currently offers free clinical breast exams, pap smears, and mammograms to eligible women enrolled in their program. To be eligible the patient must be 50 years of age or older and at or below 200% poverty. Or they can be between the ages of 40 and 49 and be a breast cancer survivor or have a mother, daughter, or sister who has breast cancer, and at or below 200% poverty. Patients should call their county health department for an eligibility interview or for more information.

Breast Self Examination Opportunity for woman to become familiar with her breasts Monthly exam of the breasts and underarm area May discover any changes early Begin at age 20, continue monthly Monthly breast self-exam or BSE is monthly examination of the breasts and underarm area by the patient where she is looking and feeling for changes. It is an opportunity for the patient to become familiar with her breasts so if there is a change, she’ll be able to detect it more quickly. Breast self-exam should begin at the age of 20 and continue monthly. In, November 2002, the United States Preventative Services Task Force found that evidence is insufficient to recommend teaching BSE. They found fair evidence that BSE caused false-positive results which increased costs to the health care system. Because there have not been any good studies done to decide the benefit/risk ratio of BSE, this group dropped BSE from its recommendations. Many doctors still teach BSE during clinical breast exams and feel there is benefit to a woman being familiar her own body. More studies need to be done.

When to do BSE Menstruating women- 5 to 7 days after the beginning of their period Menopausal women - same date each month Pregnant women – Takes about 20 minutes Perform BSE at least once a month Examine all breast tissue Despite the controversy, because some women will still want to utilize BSE, the guidelines are included in this presentation. Premenopausal women should perform BSE five to seven days following the start of menstruation. Postmenopausal women and pregnant women should mark their calendar and perform BSE the same day each month. BSE usually takes around 20 minutes and it is important that all breast tissue be examined during the self-exam. Although there have been no studies, which demonstrate a survival advantage to performing monthly BSE, it remains a cornerstone of the recommendation for early breast cancer detection by the ACS and NCI.

Why don’t more women practice BSE? Fear Embarrassment Youth Lack of knowledge Too busy, forgetfulness Why don’t more women practice BSE? Some fear finding a lump or cancer. Some are embarrassed or have difficulty touching oneself. There are taboos in some cultures about touching one’s own body. Many women think they are too young- I will worry later about cancer. Life-saving health habits formed early become a routine part of daily life and pay off later. This is why more emphasis is being place on reaching teenagers. Another big reason for not performing self-exams is a lack of knowledge of how to perform BSE, lack of confidence. Women say they are too busy or cite forgetfulness. These reasons may also be linked to fear. Since most women or their partners find breast changes, BSE can be a life saver.

Conclusion Pharmacists have a responsibility as patient advocates for breast cancer awareness In conclusion, while there remains some controversy about breast cancer, the pharmacist’s role in providing advocacy for these patients is imperative. Pharmacists should utilize their knowledge of breast cancer to educate and remind women about the importance of routine screening for this disease. Ely detection still saves lives, and we see these women regularly. So, take advantage of the opportunities available to u as a pharmacist and help save a life.