Surgery - Breast Diseases

2. Evaluation Diagnostic steps Decision to Bx Types of bx Pros/cons Bx Tech. F/U common problems Benign Lesions pathophysiology presentations Malignant Lesions W/U and Dx Therapeutic alternatives common pit-falls primary vs. adjuvant Rx pathology prognostication F/U and therapeutic efficacy Surgery - Breast Diseases

3. Evaluation • No hard and fast rules on screening mammo • all symptomatic women >30yo • within 10 yrs of first degree relative family hx • all fatty infiltrated breasts annually >40 • Other radiographic screening limited to • US in palpable abnormalities not clinically distinct in young women • W/U palp or mammo soft finding; especially in those with established risk factors

4. Self Breast Exam Women are empowered to pay attention to breast health issues by BSE “Just another way for male physicians to blame women for not finding cancer soon enough.” No study shows decrease of size at dx greater than 2.5 cm down to 1.8 cm- need to get size <1.0 cm for survival benefit

5. Evaluation • Clinical history • delineate pts risk early - use Gail Model • http://bcra.nci.nih.gov/brc/start.htm • Menarche, preg hx, breast feeding hx, family hx, hormone use • lesion characteristics • menstrual changes, dietary influences, wt loss or gain • prior breast disease hx • pt and relatives - pay close attention to proliferative • 69% successful malpractice is in + fam hx • 80% pt found lump - Remember Osler!!

6. Evaluation • PE • Pennypacker technique of palpation • three fingers; vertical strips • include axillae and lower 1/2 neck • Observation of skin • sheer curtain -fluid motion • Ck for nipple D/C • hemoccult if present; single vs. mult duct • Wait any fluid (esp. spontaneous) increases risk • mobility

7. Clinical Breast Exam • Why do it? • Purpose and goals • Breast Cancer is a common problem • Screening of pre-menopausal women poor and death rate high • Post-menopausal still 15% felt before seen on mammo • 60% diagnosed breast cancers felt before ever sent for imaging • we need to reduce size at dx to increase survival

8. Clinical Breast Exam • How to do it? • The mechanics • we are feeling to detect cancer - both sensitive and specific • dependant on scirrhous nature of most breast cancers • optimize conditions to detect differences in density • use subtle signs that imply differences in scar activity in the breast

9. Clinical Breast Exam

10. Clinical Breast Exam Thin out the breast tissue to less than 1” thick Close attention to mammographic miss locales - UIQ and LOQ Move the breast and look for differences in texture or mobility of skin relative to gland Oops decreasing evidence it works to reduce death rates In the skin, look for peau d’orange look for nipple excoriation/ Paget’s lymphatic engorgement or Cooper’s ligament shortening

11. Evaluation • Every abnormality charted and scaled • O’clock and distance to nipple • any unclear area submit to alternative exam • any suspicious on 1 exam or unclear on 2 different exams (modality or temporal) needs diagnostic evaluation - i.e.. Bx if cannot find a good reason not to. • level of suspicion based on fam hx. and other cumulative risk factors

12. Diagnostic evaluation • when unclear - Bx. • never follow more than 12 weeks without a clear commitment • Bx method depends on : • way in which lesion most crisply seen • tolerable sampling bias based on clinical situation

13. New Technologies Digital Mammo Ultrasound improvements MRI Nuclear medicine Emerging technologies

14. Technology Pixel size not yet equivalent to silver grain size GE diagnostic unit cautiously approved for screening Will allow very accurate SCBx May allow new pattern recognition to standardize reading (CAD) However post-menopause only 1/2 of unrecognized Ca B/O inaccurate reading; premenopausal Ca not detected 40% of time by mammo alone Post menopausal Film=Digital Film found mor3e solid masses Digital better with cals Fewer call backs with digital Pre-menopausal Digital is better NEJM 2005 49528 pts both D+F 0.5% + D &F Inv CA 25% D&F 10.4% F 11.3%D 21.8% never seen DCIS 10.7% D&F 5.1% F 7.5% D 7.5% not seen Digital Mammography

15. Costly technology New coils allow SCB or localization True sensitivity and specificity ? BRCA 1 (&2) have higher incidence of breast cancers not seen on mammo and MRI saves lives here. Can find 25-28% caners have MF disease – no effect on survival or eventual therapy Most insurers skeptical Very good in W/U of cystic lesions Ability to differentiate solid lesions improving Left, however, with high false + and false - rates for solid lesions Ultrasound MRI

16. Nuclear Medicine • New isotopes hold promise such as FDG, sestamibi, and C-11 thymidine • Imaging with resolution is problematic • must detect routinely @ < 10mm • More costly than MRI • New Contact and PET detectors increasing accuracy dramatically and ? Cheaper than MRI at finding MF disease

17. Experimental/ Emerging Techniques • Genetic Screening- may assess risk but not direct diagnostic efforts in individuals • Electrical Biophysical - uses properties of ionic concentration unique in normal epithelial surfaces • Ductal Based Screening and Treatment - ductal lavage and ROBE or breast endoscopy – still limited by pathology accuracy and recent data shows random PAFNA superior at identifying epithelial proliferative disease in chemoprevention (celebrex trial) • New scope and hypermethylation mapping • Lavage of non-fluid producing ducts in PAFNA +

18. Ductoscopy

19. Common Problems • Mastodynia/Mastalgia • cyclical • interfere with effects of hormones on breasts or changes menstrual hormonal pattern • non-cyclical • look for breast “mapped” causes, rx fluid retention • rx with non-steroidals • R/O non breast causes • Tietze’s syndrome, Poland’s syndrome, etc. • UCLA Study – (The Breast Journal 2005) • 86 pts eval with mammo and US for breast pain • 100% negative predictive value

20. Common Problems • Fibrocystic disease • 40% of all women in 30-50 range carry dx • cyclical lumpiness &/or tenderness • mega-cystic variant - chronic premenstrual rapidly filling cysts • fibrosis variant - multiple FA or pseudo-tumors • Beware when ca risks higher and FCD • very careful to do detailed screening

21. Common Problems • Fibroadenoma family • FA • low risk except if ductal proliferative changes in young • juvenile variant in Orientals & Blacks • 10-15% recurrence risk with excision • Lactating adenoma issues • Benign Phylloides tumors • more aggressive in local failure only

22. Common Problems • Cystosarcoma phylloides • unclear benign/malignant border • best considered a special variant of fibrosarcoma • risk for local recurrence best predicted by mitotic activity or ? Ki67 • >10 mitoses/30 HPF =Very malignant behavior • like sarcoma spread is to next capillary filter station • Rx • lumpectomy only for lowest mitotic rates • wide excision(TM) for all others & indeterminants

23. Common Problems • Nipple D/C • single duct, heme+ - 7-9% ca chance • Bx - gold standard microductectomy • galactogram pre or intra-op • nipple to 1 cm beyond obstruction • recent data suggests that routine use of breast endoscopy or galactography will double the cancer detection rate in these patients • single duct , heme- • Bx only if persistent - papilloma likely • Multiple duct, heme+ • culture and rx antibiotics x1-3 mos; bx if not response • Multiple duct, heme- • w/u prolactin axis

24. Common Problems • Infections • difficult to cure with antibiotics • acne type flora, prolonged rx stills gives failures • lactating - nurse or pump through Ab Rx • non-lactating - look for ductal blocking lesions • both pre and post Rx • Post-conservation red breast syndrome • radiation mastitis vs. anaerobic step infection

25. Common Problems • Abcess • any infection that fails to respond clinically in 3 days • w/u with US, aspirate or drain all collections • Clinical abscesses • I&D – or Aspirate, irrigate, antibiotics • W/U for ductal lesions within 1 mo of successful Rx • Peri-ductal mastitis • recurrent infection in large lactiferous ducts • may require excision to control

26. Common Problems • The funny nipple • odd crusting, asymmetric reddening, red area erupting from one of the major duct orifices • consider Paget’s until two consecutive negative bx taken of nipple-areolar complex • Inversion • only important if new and not associated with recent hormone administration • Montgomery gland problems • common inclusion cysts, hidradenitis like fungal infections

27. Breast Masses • OU 4 yr study of 414 pts presenting as breast mass primary c/o – min 6 mo f/u • No effect of family hx or risk factors on future ca dx • Probability of ca dx • 11.3% if pt found • 6.9% if physician found • 1.9% nurse/phy extender

28. Breast Masses

29. How to find it? palpation - gold std. mammo US Miralumma MRI Thermography the latest hottest research tool How big a piece do I need? surgical excision - gold surgical incisional needle incisional Mammotome, MIBB ABBI Cassi - cryocore Needle core 14G, 16G, 18G FNA Biopsy decisions

30. Biopsy decisions • commit yourself to a narrow list of acceptable diagnoses before bx • if pre-op dx important, use best single or combo of non-surgical methods first • if dx is irrelevant to excision plans, use surgical excision first • if Dx not on acceptable list, re-assess your choices - fall back on remaining best list to minimize sampling error • Don’t Forget surgical Bx

31. Gynecomastia • common in young and old • risk factors • liver disease or decreased steroid clearance • Dopamine blockers - Haldol • Dopamine del. agents-reserpine & L dopa • H2 blockers • AIDS drugs • unilateral vs bilateral • Rx - symptomatic or discreet asymmetry in gland

32. Breast Cancer • 200-230K per year; stable invasive incidence – Oops increasing to 485K/yr 2017 • 40K deaths per year; 11K preventable with annual >50 screening • another 45K DCIS/yr • probably 120K - LCIS, ALH, ADH, or other significant proliferative risk lesions • probably accounts for >30% of all Ca survivors

33. Ductal-70 % classic scirrhus mammo/sono size within 20% of path size prognosis very grade sensitive Lobular - 10-12% may be considerably larger than clinically or radiographically suspected Minor forms tubular very well diff. ductal medullary angry histopathologically but benign course if small N0 “bloody cyst” and Rad Rx adenoid cystic colloid/mucinous tumor mass tiny relative to mucus Breast CancerTypes of invasive

34. Other minor forms all sweat gland derivative types except cystosarcoma family all treated the same subtype may only effect interpretation of future systemic or contra-lateral risk Inflammatory looks like infection paucity of systemic symptoms; min Left shift on WBC High sed rate underlying breast mass Bx skin, nipple, cores may need immunohistochem to correctly differentiate tumor from lymphocytes Breast Cancer

35. Presentations Lumps ductal if hard soft - lobular,colloid,tubular, medullary, DCIS Firm patches ductal in tissue lobular Stellate mammo ductal or old lobular Calcifications ductal/ DCIS older with necrosis Nipple D/C bloody single duct Pagets disease subareolar DCIS or invasive with centripetal ductal spread Inflammatory Breast Cancer

36. 1930-1996 no change in age adjusted death rate in US from Breast Cancer 1997-2000 an 18% decrease in death rate accounted for >95% by earlier stage at diagnosis Rx successes in clinical trials not appreciated as well in nation-wide reviews Best Rx results seen with rigid evidence based The Mammo glass ceiling of 1/3 in situ to 2/3 invasive Still in best situations mammo leaves 2/3 of patients at risk for cancer death Mammo findings late calcifications usually represent obstructed ducts with a 600% increase in cross-sectional area densities depend on immunologic reaction of host to invasion with a scirrhous reaction Current State of the Art in Breast Cancer Screening and Rx

37. Breast Cancer Prevention • Increased menses = increased breast cancer risk • Breast feeding is very important to breast health • decreases pre-menopausal breast cancer frequency without affecting lifetime risk • Low fat diet, EtOH, and hormone risks?? • NSABP P-01 SERM as “THE prevention agent” • Tamoxifen - proven • Evista (raloxifen) - suspected but checkered oncologic history - poor head-to-head against Tam for therapy • Peripheral Aromatase Inhibitors - promising data from ATAC trial

38. Palpable Mass

39. Nipple Discharge

40. Mammo abnormality

41. Painful breast / FCD

42. LCIS Level of evidence - B for excision; A for tam/C for high risk f/u

43. ADH/ALH Level of evidence - B for excision; B for tam/C for high risk f/u

44. DCIS Level of evidence - A for L+R and TM; B for L alone/C for high risk f/u

45. Clinical Stage 1 or 2A All Patients with tumors >10mm and tumors 5-10mm high grade or pathologic + nodes referred for systemic rx options (I.e. hormonal or chemotherapy) Level of evidence - A for L+R and MRM; B for MRM + recon; C for no radiation in limited life expectancy; A for adjuvant systemic treatment

46. Pathologic Stage 1 or 2A All Patients referred for BHI f/u as high risk and no routine lab tests; symptomatic screening only for metastasis by ASCO guidelines All Patients with clinical indications for radiation ( LumpAx) and pathologic indications (+ or close margins; apical nodes +, etc.) referred post chemo. Benefit of Herceptin in node + cases her-2 +. Molecular testing may direct future chemo choices – NSABP retrospective . Level of evidence - A for adjuvant systemic treatment and radiation treatment; B for F/U

47. Clinical Stage 2B or 3A All Patients referred for systemic rx options (I.e. hormonal or chemotherapy) Level of evidence - A for L+R and MRM; B for MRM + recon; A for adjuvant systemic treatment; A for radiation post mastectomy for indications listed

48. Pathologic Stage 2B or 3A All Patients referred for BHI f/u as high risk and no routine lab tests; symptomatic screening only for metastasis by ASCO guidelines All Patients with clinical indications for radiation ( LumpAx) and pathologic indications (+ or close margins; apical nodes +, etc.) referred post chemo. Level of evidence - A for adjuvant systemic treatment; A for radiation indications listed ; B for f/u recommendations

49. Clinical and Pathologic Stage 3B All Patients referred for systemic rx options (I.e. hormonal or chemotherapy) Level of evidence - A for MRM, Chemo, and Radiation

50. Clinical and Pathologic Stage 4 Level of evidence - D for MRM, Chemo, and Radiation