Breast Oncology

Educational Objectives

The goal of this program is to improve the surgical management of breast cancer in the general population and during pregnancy. After hearing and assimilating this program, the clinician will be better able to:

1.   Describe the indications for digital mammography, magnetic resonance imaging, and ultrasonography in the detection and diagnosis of breast cancer.

2.   Discuss breast and partial-breast irradiation.

3.   Identify candidates for breast-conserving therapy.

4.   Review intraoperative considerations in breast-conserving therapy.

5.   List major principles guiding the treatment of the pregnant woman with breast cancer.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose. In her lecture, Dr. Holloway discusses the off-label or investigational use of a therapy, product, or de­vice.

Acknowledgements

Dr. Cole spoke at 38th Annual Postgraduate Course in Surgery, held April 16-18, 2009, in Charleston, SC, and sponsored by the Medical University of South Carolina. Drs. Holloway and Cil were recorded at Update in General Surgery 2009, held April 16-18, 2009, in Toronto, ON, and sponsored by the Department of Surgery, Faculty of Medicine, University of Toronto. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

The Evolving Role of Surgeons in Breast Cancer Management

David J. Cole, MD, Professor of Surgery, Medical University of South Carolina, Charleston

Breast cancer facts: drastic changes have occurred in management of breast cancer over past several decades; most common cancer (excluding nonmelanoma skin cancer); 5 million women <65 yr of age estimated to be at high risk in United States; second leading cause of death in women; 1 in 8 women will develop breast cancer; diagnosed in nearly 250,000 women in United States in 2008

Detection

Digital mammography: image quality superior to that of film; fast acquisition reduces need for callbacks and repeat examinations; breast receives lower total dose of radiation; better imaging of dense breasts; electronic storage possible; average cost to patient in United States $125; cost to dedicated radiology clinic $60; studies show screening mammography associated with reduced risk for mortality; number of women undergoing mammogra­phy declining; »25% of women who should have had examination within past 2 yr have not; 40% of women in lower socioeconomic categories have never had mammography

Magnetic resonance imaging (MRI): highly sensitive (detects 88%-100% of breast cancers); most helpful for women with dense breasts or strong family history of breast cancer, and for local staging of newly diagnosed disease, or detection of occult disease; does not substitute for mammography (specificity poor [high risk for false positives]); data on long-term effectiveness scarce; best method for evaluating integrity of silicone breast implants, which requires entirely different examination from screening for breast cancer

Current indications for MRI: supplemental screening for high-risk women, such as those with BRCA mutation; newly diagnosed patients (to determine extent of disease); screening of contralateral breast, especially if pa­tient considering prophylactic mastectomy; evaluation of response to neoadjuvant therapy; detection of occult primary tumors in patients initially presenting with lymph node disease; American Cancer Society indications for MRI screening of breast (2007)  —  BRCA mutation in patient or first-degree relative; lifetime risk for breast cancer >20% to 25% (as defined by models dependent on family history); history of irradiation of chest wall at young age; history of cancer syndrome or cancer syndrome in first-degree relative; indications under consideration  —  lifetime risk <25%; lobular carcinoma in situ; atypical ductal hyperplasia; heterogeneous or extremely dense breasts on mammography; personal history of breast cancer, including ductal carcinoma in situ (DCIS); inappropriate requests for MRI  —  microcalcifications on mammogram; incomplete mammo­graphic evaluation; recommendation without further justification

Ultrasonography: indications  —  diagnostic evaluation of abnormal mammography findings (unusual mass or den­sity, clustered microcalcifications, or mammographic asymmetry); clarification of findings on physical examina­tion beyond normal parenchymal changes (eg, palpable mass); role in neoadjuvant chemotherapy  —  facilitates pretreatment placement of clip in tumor bed and evaluation of tumor size before and after treatment

Genetics of breast cancer: in future, surgeons who fail to warn high-risk patients may be held liable; must connect risk to family history

Genetic abnormalities: BRCA1 and BRCA2 mutations most common; BRCA1 mutation  —  positive test result asso­ciated with 80% to 90% lifetime risk for breast cancer, 20% to 40% risk for ovarian cancer, 4-fold increase in risk for colon cancer, and 3-fold increase in risk for prostate cancer; BRCA2 mutation  —  risks for breast and ovarian cancer similar to that with BRCA1; men have £100% risk for breast cancer; also associated with mela­noma and cancer of pancreas, prostate, gallbladder, bile duct, and stomach; posttest counseling  —suggest screening for relatives of men presenting with breast cancer; warn patients that testing negative for BRCA1 or BRCA2 mutations does not eliminate risk, “it just means we didn’t define it”; incidence of BRCA mutations most common in Jewish families; ask about ovarian as well as breast cancer, and ask about cancer on both sides of family tree

Indications for genetic testing: genetic counseling should be first step, followed by blood test if appropriate; pa­tients identified as high risk can be offered increased surveillance; occasional surgical intervention (patients with BRCA1 or BRCA2 mutations often choose prophylactic mastectomy); identification of family members at high risk for cancer

Neoadjuvant chemotherapy: administered before surgery; associated with better chance for breast conservation (if tumor responds); allows oncologists to assess response to chemotherapy; use increasing, especially in patients with tumors measuring >2.5 cm; also used in women with unfavorable tumor-to-breast size ratio; not associated with increased survival rates, compared to postoperative chemotherapy

Sentinel node biopsy: indications include high-grade or extensive ductal carcinoma in situ (DCIS); opportunity to prevent missed diagnosis; if mastectomy performed in patient with multicentric disease, opportunity to identify sentinel node will be missed

Timing of neoadjuvant chemotherapy: before  —  stages axilla before intervention; facilitates planning of postopera­tive radiation therapy; after  —  avoids axillary dissection in patients with complete pathologic response; similarly, chemotherapy may alter need for postoperative radiation therapy; choice varies among institutions; superior reg­imen yet to be determined

Radiation therapy: essential component of breast conservation therapy; reduces risk for local recurrence (risk 1%-2% annually within breast; time to recurrence in vicinity of primary tumor, »33 mo; time to distant recurrence, »75 mo); tangential photon fields usually used to prevent visceral organ injury; additional dose usually adminis­tered to tumor bed

Partial-breast irradiation: controversial; approved by Food and Drug Administration in 2002; when administered postoperatively, overall rate of tumor recurrence in ipsilateral breast equals tumor occurrence in contralateral breast (ie, represents new primary tumor, not recurrence due to inadequate treatment); rates of local recurrence comparable in short-term studies (5-yr follow-up); indications  —  tumors <3 cm; node-negative disease; con­sider for DCIS or invasive carcinoma; optimal patient in early stages of disease

Partial-breast irradiation with balloon catheter placement: surgical considerations  —  skin-to-cavity distance must be >7 mm to protect skin from burns; must have good compliance between cavity and balloon; antibiotics usually administered while catheter in place; maintain close relationship with radiation oncology team; know indications for partial-breast irradiation; assess cavity size accurately; ultrasonographic evaluation helpful for assessing distance from cavity to skin

Tips on Breast-conserving Surgery

Claire Holloway, MD, Associate Professor of Surgery, Faculty of Medicine, University of Toronto, and Co-chair, Breast Site Group, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON

Benefits of breast-conserving surgery: clear psychologic, functional, and cosmetic advantages over more radical surgery

Goals: to completely remove tumor with clear margins and preserve as much normal breast parenchyma as possible

Candidates: must be candidates for postoperative radiotherapy; primary contraindications include previous irradia­tion of breast, history of collagen vascular disease, and disease extending beyond one quadrant

Carriers of BRCA1 or BRCA2 mutations: recent study shows high rate of new ipsilateral tumors 4 to 5 yr after con­servative therapy, compared to noncarriers; time frame suggests new primaries, rather than recurrences of previ­ous tumor

Preoperative identification of tissue to excise: requires determining extent of disease within breast; helpful tech­niques include magnification views of calcifications surrounding tumor and MRI if breasts dense or tumor multifo­cal; biopsy other suspicious areas to determine need for excision; evaluate contralateral breast (occult primary tumors found in 3%-4% of patients); identify all lesions in both breasts for comprehensive excision during surgery; standard mammography often helpful

Intraoperative considerations: good incisions provide good access and optimal cosmesis; should fit within ellipse (in case mastectomy required or if recurrence develops); discuss wire placement with radiologist; passing hook through tumor recommended so thick portion of wire remains in lesion; direct medial-lateral or superior-inferior orientation preferred so that wire’s trajectory known; also provides guidance for good margins; bracketing wires helpful for segmental or multifocal lesions (discuss with radiologist); if lesion localized via ultrasonography, have radiologist mark location on skin; with diffuse disease, use diagram that maps locations to be excised; avoid cau­tery artifact (distorts cytologic features and interferes with accurate pathologic interpretation of specimen)

Handling and processing of specimen: orient with clips or sutures; at University of Toronto, conformation main­tained by embedding specimen in agar gel from which whole- mount slices can be taken; helps with margin evalu­ation; ask radiologist not to compress specimens excessively; share clinical information with pathologist to facilitate interpretation; advise when multiple lesions present; if pathology report discordant with results of core bi­opsy, ask whether pathologist saw core needle biopsy track within specimen to confirm removal of target area; in­form pathologist if lumpectomy performed for calcifications

Management of Breast Cancer During Pregnancy

Tulin Cil, MD, Assistant Professor, Department of Surgical Oncology, Faculty of Medicine, University of To­ronto, ON

Pregnancy-associated breast cancer: diagnosed during pregnancy, up to 1 yr after delivery, or any time during lac­tation; affects »1 in 3000 pregnancies; second most common malignancy in pregnant women, after cervical can­cer; of breast cancer patients <40 yr of age, 10% pregnant at time of diagnosis; incidence predicted to rise as more women delay childbearing

Presentation: painless palpable mass; diagnosis through clinical examination often difficult, due to normal changes associated with pregnancy and lactation; clinical breast examination recommended at first prenatal visit; average diagnostic delay 1 to 2 mo

Pathology: histologically, most cases invasive ductal carcinomas; decreased rate of estrogen and progesterone re­ceptor positivity; HER2/neu status currently uncertain; patients present with higher-stage disease and larger tu­mors, and more likely to be node-positive than nonpregnant patients; 2.5 times more likely to have metastatic disease at time of presentation

Imaging techniques: ultrasonography “very effective” for examining palpable lesions and differentiating between solid and cystic lesions; sensitivity of mammography decreased, but useful for evaluating extensive microcalcifica­tions; fetal exposure to radiation minimal with appropriate abdominal shielding; MRI not recommended for routine imaging of pregnant patients; in work-up for metastases, follow guidelines for nonpregnant patients (chest x-ray, abdominal ultrasonography, and low-dose bone scanning all acceptable)

Tissue diagnosis: pregnancy-related changes in breast tissue may increase risk for false-positive fine-needle aspira­tion (warn cytopathologist); core needle biopsy  —  gold standard for tissue diagnosis in pregnant patients; provides definitive diagnosis and shows hormone and HER2/neu receptor status; increased breast vascularity and lactational changes increase potential for complications

Principles of treatment: goals are to achieve local control and prevent systemic metastasis; treatment individualized, depending on stages of gestation and disease, and patient preference; multidisciplinary approach imperative; team should include high-risk obstetrician, as well as surgical and medical oncologists; psychosocial support for patient and family also important; termination of pregnancy does not improve survival and not routinely recom­mended; second and third trimesters safest time for surgery (risk for spontaneous abortion low); begin fetal mon­itoring after 24 wk; consider appropriate positioning when operating; modified radical mastectomy typical surgical approach in past; breast-conserving surgery now used increasingly, with postsurgical chemotherapy and radiation therapy after delivery; some evidence of increased rate of locoregional recurrence 5 yr after breast-con­serving surgery, compared to mastectomy

Sentinel lymph node biopsy: not systematically evaluated in pregnant patients; risk for fetal irradiation low, but blue dye mapping agent mutagenic (contraindicated in pregnancy); biopsy offered to pregnant patient only after thorough risk-benefit discussion with patient; in study of 10 patients, no adverse outcomes noted in mother or fe­tus

Medical management: chemotherapy beyond first trimester does not increase risk for fetal malformation, but does cause maternal and fetal myelosuppression; discontinued 3 to 5 wk before delivery; most regimens based on an­thracycline (methotrexate contraindicated); hormonal therapies ineffective because most tumors negative for hor­mone receptors; tamoxifen contraindicated; safety of aromatase inhibitors during pregnancy not demonstrated; trastuzumab (Herceptin) not well studied (case reports of use available)

Prognosis: historically considered poor; some age- and stage-matched studies show similar survival rates in pregnant and nonpregnant patients; other studies suggest worse survival, especially if disease advanced

Future pregnancies: traditionally, patients advised to wait 2 yr after treatment before conceiving another child; mul­tiple studies suggest that chances of survival similar to, if not better than, those of nonpregnant women matched for age and disease stage; subsequent pregnancy may improve survival chances (“healthy mother effect”)

Suggested Reading

Beitsch PD et al: The surgeon’s role in breast brachytherapy. Breast J 15:93, 2009; Gentilini O et al: Breast cancer diagnosed during pregnancy and lactation: biological features and treatment options. Eur J Surg Oncol 31:232, 2005; Halaska MJ et al: Presentation, management and outcome of 32 patients with pregnancy-associated breast cancer: a matched controlled study. Breast J 15:461, 2009; Khera SY et al: Pregnancy-associated breast cancer patients can safely undergo lymphatic mapping. Breast J 14:250, 2008; Mann RM et al: The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 119:415, 2010; Molckovsky A, Madarnas Y: Breast cancer in pregnancy: a literature review. Breast Cancer Res Treat 108:333, 2008; Moran MS et al: The Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) treated with breast conservation treatment (BCT): analysis of clinical-pathologic features, long-term outcomes, and molecular expression of COX-2, Bcl-2, and p53 as a function of histology. Breast J 15:571, 2009; Santiago RJ et al: Fifteen-year re­sults of breast-conserving surgery and definitive irradiation for Stage I and II breast carcinoma: the University of Pennsylvania experi­ence. Int J Radiat Oncol Biol Phys 58:233, 2004; Saslow D et al: American Cancer Society guidelines for breast screening with MRI as adjunct to mammography. CA Cancer J Clin 57:75, 2007; Smith BD et al: Accelerated partial breast irradiation consensus state­ment from the American Society for Radiation Oncology (ASTRO). J Am Coll Surg 209:269, 2009; Thomas J et al: Radiological and pathological size estimations of pure ductal carcinoma in situ of the breast, specimen handling and the influence on the success of breast conservation surgery: a review of 2564 cases from the Sloane Project. Br J Cancer January 5, 2010 [Epub ahead of print]; Yo­shida T et al: True Recurrences and New Primary Tumors Have Different Clinical Features in Invasive Breast Cancer Patients with Ipsilateral Breast Tumor Relapse After Breast-Conserving Treatment. Breast J December 21, 2009 [Epub ahead of print].