Karen degenevieve MSN, FNP, BC

Transcription

1 Karen degenevieve MSN, FNP, BC Become more comfortable treating common breast complaints. Discuss recent controversial screening recommendations. Discuss oral medications used in breast cancer prevention and treatment. Recognize patient populations who should have genetic testing for BRCA 1&2

2 Evaluation of breast complaints requires a vigilant and systematic approach to ensure that cancers are diagnosed and treated promptly and benign breast disease receives appropriate attention and care. It is important to keep in mind that the missed diagnosis of breast cancer is one of the most frequent causes of malpractice claims. Evaluation of breast pain needs to determine normal physiology verses pathology. Breast pain is the most common breast symptom prompting evaluation. While both breast pain and cancer may occur in the same patient, data is conflicting on whether the presence of breast pain increases risk for breast cancer. Cyclical breast pain verses non cyclical breast pain. Cyclical mastalgia is usually hormonal. Fibrocystic breast changes and chronic cystic mastitis are benign conditions that are common causes of breast pain that clinical exam describes as nodular, sensitive breasts.

3 Noncyclical breast pain does not follow the usual menstrual pattern and is more likely to be unilateral. Causes include postmenopausal HRT, ductal ectasia, mastitis, breast abscesses, inflammatory breast cancer, post breast surgery, thrombophlebitis, and a variety of medications. (hormones, some antidepressants, cardiovascular agents, and antibiotics) Extramammary pain includes chest wall pain, spinal or paraspinal problems, trauma, post thoracotomy syndrome. Burning pain is typical of nerve root pressure and can be radicular and may present with hypersensitivity Bilateral or milky discharge (galactorrhea) is benign and most commonly occurs after childbearing. It generally subsides within one year after cessation of nursing, but can occasionally last much longer. Galactorrhea may also be associated with hypothyroidism, and prolactin-producing pituitary tumors as well as medications, ( tricyclic antidepressants and antipsychotics. Prolactin levels under 50 are less likely to suggest pituitary adenomas.

4 If discharge is bilateral and milky, and it has been over one year since nursing, a prolactin level is ordered and if over 100 an MRI of brain should be done to rule out prolactin producing pituitary adenoma. Always check medication list for tricyclic antidepressants, and antipsychotics. You may need endocrinology referral with pituitary adenomas. Spontaneous, clear, colored, or bloody unilateral nipple discharge from one duct is suspicious and requires investigation. Discharge that is only seen with stimulation is generally not worrisome and usually stops when the stimulation stops. While nipple discharge may be due to benign conditions such as a papilloma, cystic changes in the breast, or duct ectasia (dilatation), it may also be due to papillary cancer or DCIS and full workup is indicated.

5 If discharge is spontaneous, unilateral and physical exam is otherwise normal, diagnostic mammogram and ultrasound are ordered, to look for underlying abnormalities that may require surgical biopsy. If no abnormalities are found on physical exam or imaging and the discharge persists, surgical biopsy with terminal duct excision is indicated Mammographic simple cysts can be aspirated, either in the office or under ultrasound guidance. Complex cysts have a 10% chance of malignancy and should be sent to a surgeon.

6 Non bloody fluid should NOT be sent for analysis as it will be negative Study showed that out of 7,000 fluid specimens from breast cysts 0 were positive Bloody fluid shows 7% were cancerous, send for analysis. Complex cysts need biopsy Any skin lesion can be found on the skin of the breast but the most common complaints are skin discoloration, eczematous changes such as scaling, ulceration or crusting, skin dimpling, thickening, or edema. Redness and ulceration of the skin around the nipple can be seen in Paget disease, which is associated with underlying malignancy often without an associated breast mass or mammographic abnormality.

7 Erythema associated with skin thickening or edema is worrisome for inflammatory breast cancer. A skin punch biopsy can be performed in the office with local anesthesia. If the physical examination is otherwise negative and tenderness does not preclude compression, a diagnostic mammogram is performed to rule out an underlying malignancy. One breast is smaller than the other If this is a new finding, investigate If this is persistent from puberty, it is a normal variant

8 Inverted nipples that are a new finding, needs work up If inverted nipples have always been that way, it is a normal variant Ask about the history Breast masses may be palpable or visualized on mammogram. Fibroadenomas and cysts are the most common causes of breast masses. Findings in benign breast disease can mimic those in cancer since breast tissue in normal women is often somewhat lumpy.

9 Few breast cancers are missed with triple diagnosis: Clinical exam Mammogram FNA Diagnostic mammogram Ultrasound if indicated Know your local surgeon and refer Follow up with patient

10 Any breast complaint other than cyclic premenopausal pain without clinical evidence of an abnormality, should get diagnostic mammogram and ultrasound if indicated. Referral to a surgeon. Breast Cancer DIAGNOSIS: Ductal carcinoma in situ. FINDINGS: Right craniocaudal view shows a 4 mm nodule present in the retroareolar region, slightly lateral and 4 cm deep to the nipple. The nodule is slightly lobulated and has minimal spiculation. The craniocaudal magnification view confirms this finding and shows that no calcification or architectural distortion is present. DISCUSSION: Pathology found the biopsy specimen to contain duct carcinoma in situ. In addition, two small foci of well-differentiated invasive ductal carcinoma were also present. The duct carcinoma in situ extended to the surgical margin focally. Some of the in situ carcinoma showed necrosis but no calcification was associated with the lesion.

11 Excellent characterization with better sensitivity than mammograms especially in early age group. Detects multicentric lesions more effectively ASCO in 2007 recommended screening MRI in women with high risk familial breast cancer, including BRCA 1 and 2 MRI equipment that is specifically designed for breast and hopefully, the reduction in cost will help in use as screening. Useful test also for achieving negative margins and assessing response to treatment in the neoadjuvant setting. MRI Screening Test (Women with High Familial and Genetic risk; n=1909) Test Sensitivity Specificity CBE 16% 97% Mammo 33% 95% MRI 79.5% 90% (Kriege et al; N Engl J Med 2004;351:427-37

12 Can determine whether a breast mass is a simple or complex cyst, or solid mass. Most useful in the following circumstances: Women under 35 Evaluation of non palpable mass seen on screening mammogram Mass that is too small or deep for aspiration Persistent thickening or asymmetry with negative radiologic findings. Patients with overwhelming fear of breast cancer. Patients with strong family history of breast cancer. Refer, refer, refer, refer

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14 Increased density Irregular margins Spiculation Accompanying clustered irregular microcalcifications Mammograms miss 10-20% of clinically palpable breast cancer. Negative mammograms should not stop further investigation if a lump is present.

15 Stereotactic needle biopsy or open biopsy of a mass that produces ductal hyperplasia with atypia will need close F/U. The use of Tamoxifen in these women may decrease the chance of breast cancer by about 43% in 15 years. The 2 most important risk factors for the development of breast cancer are age and gender. The risk increases with age; however, greater than 70% of women diagnosed with breast cancer will have no identifiable risk factors. That is why screening is important.

16 Risk factors Risk Factors for Breast Cancer Risk Factor Relative Risk Average Risk 1.0 Age at Menarche (<12 yr) (1.25) Hormone Replacement Therapy (1.25) 2 nd degree relative (1.75) Age at menopause (>55 yr) (1.75 Breast biopsy (any histology) (1.75) Age at first live birth (>30 yrs) (2.0) Atypical Hyperplasia (4.0) Age (>50) 6.0 First degree relative (10.0) (BRCA 1 or 2) (Nat. Cancer Inst, Bethesda, MD USA, 2003)

17 Surgery Neoajuvant chemotherapy for large tumors and inflammatory breast cancers. Breast conserving surgery requires post chemotherapy radiation. Adjuvant chemotherapy for high risk cancers. Adjuvant endocrine therapy with Tamoxifen or SERM s

18 ER/PR status, positive or negative Her 2 neu status, 1+, 2+, 3+, (3+ is positive) Triple negative breast cancer Inflammatory breast cancer Paget s disease of the breast Neglected breast cancer that becomes inflammatory

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23 Cancerous breast tissue from ER/PR +,node negative patient is tested. Gives recurrence rates and risk % Low recurrence rate and risk can consider no chemotherapy, just adjuvant SERM for 5 years. The goal of adjuvant endocrine therapy is to prevent breast cancer cells from receiving stimulation from endogenous estrogen. Tamoxifen in ER + breast cancer reduces the 5 year recurrence rate by 40% and death by 35%. Tamoxifen is a selective estrogen receptor modulator (SERM)

24 Dose is 20 mg daily X 5 years after completion of chemotherapy and radiation. The efficacy is dependent on treatment compliance and potential for tamoxifen resistance and/or drug interactions. It also acts by competitive antagonism of estrogen at estrogen receptor. It also acts as partial estrogen agonist. Antiestrogenic on breast tissue and uterus Estrogenic on bones Increased risk of uterine cancer and thromboembolic events Can be used in both postmenopausal and premenopausal women. STAR trial showed equal efficacy between Evista and Tamoxifen.

25 Hot flashes Vaginal discharge Thromboembolic events Endometrial cancer Stroke Retinopathy and cataract formation Elevated LFT s rare Other CYP2D6 inhibitors Celebrex, remeron, elavil, reglan, cimetadine, timolol, propranolol, etc. SSRI s Paxil, prozac, zoloft, celexa, and effexor. In theory, these drugs may inhibit antiestogen effects

26 Are generally preferred as they are more effective in preventing breast cancer recurrence. Suppresses plasma estrogen levels by inhibiting aromatase, the enzyme responsible for synthesizing estrogens from androgenic substrates. Anastrozole, letrozole, and exemestane Bone loss Fewer SE s than Tamoxifen 45% of women experience joint pain Nausea, fatigue, mood disturbances, cataracts, and ischemic cardiovascular disease similar to tamoxifen. SSRI s should be used with caution.

27 Anastrozole (Arimidex) 1 mg daily Letrozole (Femara) 2.5 mg daily Exemestane (Aromisin) 25 mg daily

28 Identifying and Managing Hereditary Breast and Ovarian Cancer Syndrome Characterized by significantly increased risks for breast and ovarian cancer Most cases are caused by a BRCA1 or BRCA2 mutation Clinical testing is available to identify individuals with mutations AJHG 1998;62: JCO 2002;20:

29 Will not identify testing candidates No paternal history No extended family- does NOT ask about 2 nd degree relatives No ovarian cancer history Incorrect estimate of HBOC cancer risks Under/over estimate of breast cancer Ovarian cancer not addressed 100 Positive for deleterious BRCA mutation Cancer Risks % 50 Risk based on family history Negative for familial BRCA mutation Age (Years) Reprinted with permission from Ponder B: Genetic Testing for Cancer Risk. Science 1997; 278: Copyright 1997 American Association for the Advancement of Science

30 Breast Cancer BRCA1: more likely to be ER/PR (-) Basaloid phenotype BRCA2: more likely to be ER/PR (+) Prognosis appears to be the same as for sporadic breast cancer Ovarian Cancer Predominantly papillary serous Lancet 1998;351: NEJM 1996;335: JAMA 2000;283: JCO 2000;18:119s-24s Cancer 2003;97: JCO ; 23(8): Risk of Cancer (%) % Up to 50% 8% Up to 87% <1% Up to 44% General Population BRCA Mutation Breast cancer by age 50 Lancet 1994;343: NEJM 1997;336: AJHG 2003;72: Breast cancer by age 70 Ovarian cancer by age 70 AJHG 1995;56: Science 2003: JCO (8): NCI 2005

31 60 Up to 64% General Population BRCA Mutation Risk of Cancer (%) Up to 3.5% Up to 27% Up to 11% 0 Breast Cancer after 5 years Breast Cancer by age 70 Ca Epi Biomarkers Prev. 1999;8(10): JNCI 1999;15: JCO 1998;16: Lancet 1998;351: JCO 2004;22: Lancet 1994;3343:692-5 Gynecol Oncol Jan;96(1): fold increased risk compared to noncarriers No effective ovarian cancer screening Prophylactic bilateral salpingo-oophorectomy recommended (NCCN) J Clin Oncol : Gynecol Oncol Jan;96(1):

32 Risk of Cancer (%) % 15% 20% General Population BRCA Mutation* <1% Breast Cancer by age 80 Prostate Cancer by age 80 *Risks refer to BRCA2 mutation carriers. Risks for male BRCA1 mutation carriers are less characterized JCO 2004;22: NCI 2005 Risk of Cancer (%) % 2-4% General Population BRCA Mutation <1% 1% Pancreatic cancer by age 80 Melanoma by age 80 JNCI 1999;15: JNCI 2002; J Med Genet Sep;42(9):711-9

33 Surveillance Chemoprevention Prophylactic surgery *Individual risk reduction may vary based on personal health history JAMA 2000;283: Procedure Age to begin Frequency Breast self-exam 18 yrs Monthly Clinical breast exam 25 yrs Twice a year Mammography 25 yrs Yearly MRI 25 yrs Yearly Cancer 2004;100: NEJM 2004;351:427-37

34 Affected BRCA carriers: 50% decrease for contralateral breast cancer Unaffected BRCA2 carriers: 62% decrease Unaffected high-risk: 45% decrease Aromatase inhibitors are currently under investigation Int J Cancer. 2006;118(9): Lancet 2000;356: JAMA 2001;286: JNCI 1998; 90: Total (simple) mastectomy more effective than subcutaneous mastectomy NEJM 2001;345: JNCI 2001;93: JCO 2004;22: BJC 93(3):287-92

35 CA-125 Pelvic exams Transvaginal ultrasound Additional screening techniques under investigation due to limited efficacy of current options J Clin Oncol Mar 10; 23(8): Up to 60% risk reduction for ovarian cancer Current literature supports there is no evidence that current low-dose oral contraceptive formulations increase the risk of early onset breast cancer for mutation positive individuals NEJM 1998; 339:424-8 NEJM 2001;345: JNCI 2002;94: Ca Epi Biomarkers Prev Feb;14(2):350-6

36 ~96% ovarian cancer risk reduction in BRCA carriers Can reduce breast cancer risk by up to 68% for both BRCA1 and BRCA2 mutation carriers JAMA. 2006;296: Clin Oncol Mar 10;23(8): NEJM 2002;346: Prevalence of occult tumors: up to 23.5% fallopian tube ovarian cancer Removal of both ovaries and fallopian tubes is recommended Careful pathological examination after BSO even if gross pathology is normal Gynecol Oncol. 2002;87(1):52 Br J Cancer 2004; 90: NEJM 2002;346: Am J Surg Pathol 2001;25: JCO ;23(1): Gynecol Oncol Aug;98(2):179-81

37 Breast Site Prostate Procedure Clinical breast exam Breast self-exam Mammography Prostate-specific antigen testing Digital rectal exam Frequency Yearly Monthly Based on Clinical Findings Yearly Yearly Up to 22% of breast cancer patients are at-risk for hereditary breast and ovarian cancer syndrome Mutations in BRCA1 and BRCA2 dramatically increase the risks for breast and ovarian cancer Specific medical management options are available to reduce cancer risks Cancer 2002 Jan 15;94(2):305-1 Cancer 2005 Nov ;104(9): J Clin ONcol 2005 Mar 10; 23(8):

38 Breast cancer before age 50 Ovarian cancer at any age Male breast cancer at any age Multiple primary cancers Ashkenazi Jewish ancestry Relatives of a BRCA mutation carrier Cancer 2005 Dec 15;104(12) Science 2003;302:643-6 American Society of Breast Surgeons, June 12, Family History Considerations One-half of BRCA carriers inherit the mutation from their father Ovarian cancer is a very important indicator Early onset breast cancer is more important than the number of affected family members Science 2003:302(5645):643-6

39 Family History Patient s History No breast cancer <50 or ovarian cancer Breast cancer <50, no ovarian cancer Ovarian cancer in one relative, no breast cancer <50 No breast or ovarian cancer 2.8% 4.5% 5.6% Breast cancer <50 6.8% 15.8% 16.9% Ovarian cancer, no breast cancer 8.8% 23.1% 21.1% Family History Patient s History No breast cancer <50 or ovarian cancer Breast cancer <50, no ovarian cancer Ovarian cancer in one relative, no breast cancer <50 No breast or ovarian cancer 6.9% 13.7% 15.6% Breast cancer < % 24.2% 38.8% Ovarian cancer, no breast cancer 22.2% 37.0% 42.0%

40 Women with DCIS should be considered potential members of HBOC families Especially women diagnosed <50 and in the presence of other red flags Family History - Includes at least one first or second degree relative PATIENT HISTORY No breast cancer <50 or ovarian cancer in anyone Breast cancer <50 in one relative; no ovarian cancer in anyone Breast cancer <50 in more than one relative; no ovarian cancer in anyone Ovarian cancer at any age in one relative; no breast cancer <50 in anyone Ovarian cancer in more than one relative; no breast cancer <50 in anyone Breast cancer <50 and ovarian cancer at any age DCIS <50, no invasive breast or ovarian cancer 4.3% 8.6% 6.8% 8.6% 15.7% 9.3% JAMA ;293(8):964-9 Positive for a deleterious mutation No mutation detected Mutation previously identified in the family No known mutation in the family Genetic Variant of Uncertain Significance

41 BRCA-associated cancer risks 50% chance for first degree relatives to have the same mutation Children Siblings Parents Test relatives for identified familial mutation General population cancer risks if no cancer history on the other side of the family Avoid unnecessary screening/surgery

42 Rules out most causes of HBOC Manage based on the negative result and personal and family cancer history Clinical significance not yet known Manage based on personal and family cancer history May be further clarified by testing of specified family members molecular or functional analysis population studies

43 Benefits Allows for individualized medical management Accurate risk assessment Alleviates uncertainty and anxiety Limitations Genetic testing for BRCA1 and BRCA2 does not identify all causes of hereditary breast or ovarian cancer. All major carriers provide coverage for genetic testing Established guidelines Medicare Most major carriers

44 Federal and state laws prohibit the use of genetic information as a pre-existing condition Federal HIPAA legislation The majority of states have additional laws Over 175,000 clinical tests performed to date No documented cases of genetic discrimination AJHG 2000;66: ACCC- Association of Community Cancer Centers AMA- American Medical Association ASBS- American Society of Breast Surgeons ASCO- American Society of Clinical Oncology NCCN- National Comprehensive Cancer Network ONS- Oncology Nurses Society SGO- Society of Gynecologic Oncologists SSO- Society of Surgical Oncology USPSTF- U.S. Preventive Services Task Force

45 Available through healthcare providers Federally-certified clinical laboratory Turnaround time ~3 weeks Expedited processing available Insurance preauthorization services available 1. Screen for Red Flags 2. Discuss genetic testing options 3. Establish appropriate medical management plan

46 Please remember that the missed diagnosis of breast cancer is one of the most frequent causes of malpractice claims. Gail Model Risk assessment tool: