Breast Cancer Treatment: An Evidence-based Review Judith Luce, M.D.

Patient One  Your 45 yo patient had her first screening mammogram and was found to have abnormal calcifications  An ultrasound guided core biopsy was performed and show DCIS (ductal carcinoma in situ).  What do you tell her about treatment?  What about life expectancy?

Ductal Carcinoma In Situ: What is the Risk?  DCIS is not invasive cancer: however it can recur in the breast as invasive cancer about half the time  Recurrence risk is dependent on Age of the patient at diagnosis Age of the patient at diagnosis Histology of the DCIS: Histology of the DCIS: Comedonecrosis, high grade are risk factorsComedonecrosis, high grade are risk factors Extent of disease: larger=higher risk Extent of disease: larger=higher risk Extent of resection: negative margins Extent of resection: negative margins

Age Affects DCIS Recurrence Silverman, Buchanan Breast, 2003

Treatment Options for DCIS  Do nothing. Lifetime risk of invasive cancer ranges from 50%. May be a choice for small low grade DCIS in older pts  Remove all of the DCIS Lumpectomy if feasible Lumpectomy if feasible Mastectomy if not: lowest odds of recurrence Mastectomy if not: lowest odds of recurrence  Add radiation to the breast Reduces recurrence risk by at least 50% Reduces recurrence risk by at least 50% No real risk of lymphedema; other risk same No real risk of lymphedema; other risk same  Add hormone therapy Check for ER positivity Check for ER positivity Reduces risk by about 20% Reduces risk by about 20% “Usual” duration five years “Usual” duration five years

Patient Two  A 55 yo diabetic woman presents with a small mass in her LUOQ. The FNA is “ductal carcinoma”. You can’t feel any axillary masses, and the mass itself is about 4 cm. She’s frantic.  Should you do a staging workup?  What do you tell her about the initial treatment?  What do you tell her about prognosis?

Assessing the Risk of Invasive Breast Cancer: Staging  Spread of breast cancer to adjacent lymph nodes indicates high risk of distant spread of cancer If no further therapy, 50% or more will recur with metastatic cancer If no further therapy, 50% or more will recur with metastatic cancer  Size of tumor indicates risk of relapse: higher “T” stage indicates higher risk  Certain subtypes are higher risk: Inflammatory breast cancer very high Inflammatory breast cancer very high Tubular, medullary carcinomas very low Tubular, medullary carcinomas very low

Assessing the Risk of Diagnosed Breast Cancer: Staging  Staging is performed surgically: Removal of entire mass Removal of entire mass Sampling of lymph nodes—sentinel node Sampling of lymph nodes—sentinel node  Higher risk patients staged with CT scans of abdomen and chest CT scans of abdomen and chest Bone scan Bone scan Little role: brain scan, PET scan Little role: brain scan, PET scan

Selection of Adjuvant Therapy for Invasive Breast Cancer: a Risk-Benefit Equation  Prognostic factors: what is the risk of relapse? Patient characteristics: age, menopause, race Patient characteristics: age, menopause, race Disease characteristics: size, histology, nodes Disease characteristics: size, histology, nodes Biomarkers: ER/PR, growth fraction, Her2/neu, Oncotype Biomarkers: ER/PR, growth fraction, Her2/neu, Oncotype  Predictive factors: what will affect the choice of therapy? Patient characteristics: age, comorbid illness, performance status Patient characteristics: age, comorbid illness, performance status Biomarkers: ER/PR, Her2/neu, Oncotype, possibly growth fraction Biomarkers: ER/PR, Her2/neu, Oncotype, possibly growth fraction  Risk/benefit: will the absolute magnitude of the benefit exceed the long term risks?

Surgery for Invasive Breast Cancer  Lumpectomy +radiation therapy = mastectomy Slight difference in local recurrence rate, esp younger women Slight difference in local recurrence rate, esp younger women Who is a lumpectomy candidate? Who is a lumpectomy candidate? Woman wishes to preserve breast, willing to get radiationWoman wishes to preserve breast, willing to get radiation Lump less than 5 cm diameter, mobile, not in centerLump less than 5 cm diameter, mobile, not in center Breast would look acceptable after resectionBreast would look acceptable after resection Margins must be clear of both invasive and in situ cancerMargins must be clear of both invasive and in situ cancer No other suspicious masses in breastNo other suspicious masses in breast No inflammatory breast cancerNo inflammatory breast cancer  New developments: core biopsies, laser removal need to demonstrate completeness of excisionneed to demonstrate completeness of excision

Breast Surgery: Sentinel Node Biopsy for Staging of the Axillary Nodes  What is it? Radionuclide and dye-assisted identification of the first node area, local bx  If nodes negative and sampler proficient, then predicts negative axillary dissection  No need for axillary dissection if negative—spares patient the risk of lymphedema  No need to do this if mastectomy planned, if high likelihood of positive nodes, if tail of breast involved, if going to treat an older woman with adjuvant Tamoxifen anyway  Costlier, more time- and labor-intensive

Patient Two….  She comes back to ask your advice about her surgical choices—mastectomy and reconstruction versus lumpectomy. She says she’s “scared” of radiation.  What are the pros and cons of the two approaches?  What are her patient risk factors for one or the other?

Breast Reconstruction for Women with Mastectomy  Tissue reconstruction: use of autologous flaps for reconstruction Abdominal flaps “TRAM” flap—rectus abdominis Abdominal flaps “TRAM” flap—rectus abdominis Latissimus dorsi flaps Latissimus dorsi flaps Free flaps: DIEP flap—require vascular anastomosis Free flaps: DIEP flap—require vascular anastomosis Can be done any time; Calif law requires insurance to cover cost including contralateral reductions, mastopexy Can be done any time; Calif law requires insurance to cover cost including contralateral reductions, mastopexy  Implants: best evidence suggests that silicone is actually safe; still are problems with any implant Puncture—forms intense inflammatory reaction and more lumps if silicone, collapses if saline. Usually retropectoral, so problems less vs augmentation Puncture—forms intense inflammatory reaction and more lumps if silicone, collapses if saline. Usually retropectoral, so problems less vs augmentation “Capsule” formation—alters shape, consistency “Capsule” formation—alters shape, consistency

Radiation Therapy for Primary Invasive Breast Cancer  As consolidation for lumpectomy patients Small effect on survival —1-2%? Small effect on survival —1-2%? Affects breast outcome: 30+% risk of local failure in younger women without XRT Affects breast outcome: 30+% risk of local failure in younger women without XRT May not be necessary in oldest women: risk of local failure with Tamoxifen, over 70, less than 5% in studies May not be necessary in oldest women: risk of local failure with Tamoxifen, over 70, less than 5% in studies  After mastectomy for high risk patients Large tumor, inflammatory, bulky nodes Large tumor, inflammatory, bulky nodes Controversial impact on survival (see figure) Controversial impact on survival (see figure)

Long Term Hormone Therapy Effects  Tamoxifen effects better researched  Tamoxifen does not cause menopause, but it definitely increases the symptoms of menopause— most common reason women stop  Serious risks due to agonist effects: thrombosis (strongly age-related, includes stroke, MI, PE, DVT) thrombosis (strongly age-related, includes stroke, MI, PE, DVT) endometrial Ca for postmenopausal women (2-3X increase in risk) endometrial Ca for postmenopausal women (2-3X increase in risk) Both risks disappear when drug is stopped—aromatase inhibitors do not have these effects at all Both risks disappear when drug is stopped—aromatase inhibitors do not have these effects at all  Tamoxifen does protect bones: castration and aromatase inhibitors do not

Patient Perspectives on Adjuvant Therapy for Breast Cancer  Women need help with decision-making Often find differing opinions among physicians Often find differing opinions among physicians Are usually more satisfied if they have participated Are usually more satisfied if they have participated Reliable sources of information are increasing Reliable sources of information are increasing “Utility” is highly personal, variable, and persons being asked in current studies are not representative “Utility” is highly personal, variable, and persons being asked in current studies are not representative  Diagnosis of breast cancer induces stress Women recover with time Women recover with time Women with premorbid problems are most likely to need and benefit from support Women with premorbid problems are most likely to need and benefit from support

Long Term Follow-up After Breast Cancer  Women who have had breast cancer are at lower risk for new breast cancer event if treated systemically  Women who have been treated with 5 years of Tamoxifen have a reduced new opposite breast cancer risk of about 40%; AI similar.  Mammography annually, breast exam every 6-12 months is recommended by all experts  Routine CT or bone scanning is NOT recommended—no survival benefit  Most experts use routine laboratory tests and occasional chest x-rays as screening tests  Most important aspect is careful history and physical exam

Summing Up Evidence-based therapies for DCIS and invasive breast cancer: Surgical excision—less is more Radiation therapy—preserves breasts Chemotherapy—younger, higher risk Hormone therapy—ER+ all ages Patient care includes education, support, long term follow-up