Local management of invasive breast cancer
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Local Management of Invasive Breast Cancer. By Steven Jones, MD. Connecting with the patient is the best part of medicine. We ’ re artists, not engineers. Epidemiology of Breast Cancer. 232,340 American women diagnosed each year. 39,620 die each year from the disease

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Epidemiology of breast cancer
Epidemiology of Breast Cancer

  • 232,340 American women diagnosed each year.

  • 39,620 die each year from the disease

  • Lifetime risk through age 85 is 1 in 8, or 12.5%

  • 2nd leading cause of cancer deaths among US women, after lung cancer

  • Leading cause of death among women age 40-55


Staging recommendation prior to primary therapy
Staging Recommendation prior to primary therapy

  • History and physical

  • Liver function tests

  • Breast imaging: ipsilateral and contralateral breasts

    • Mammogram

    • U/S

    • MRI

  • Axillary imaging

    • U/S

    • MRI


  • Mri for local regional staging
    MRI for Local-regional Staging

    Pros:

    Cons:

    With adjuvant therapy local failure low – 6%

    Too many mastectomies

    Some data demonstrate no difference in local failure rates

    • Changes surgery 20%

    • Multifocal- 3.6%

    • Multicentric – 4.4%

    • Contralateral – 1.8%


    Mri pre op
    MRI Pre-op

    • Diagnostic dilemma

    • BRCA 1 / 2 known or suspected carriers wishing BCT

    • Occult malignancy presenting with axillary mets



    CRITERIA FOR REFERRAL FOR GENETIC COUNSELING OF INDIVIDUALS AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST CANCERa,b

    • Personal history of breast cancer diagnosed≤ 40

    • Personal history of breast cancer diagnosed≤ 50 and Ashkenazi Jewish ancestry

    • Personal history of breast cancer diagnosed≤ 50 and at least one first- or second-degree relative with breast cancer ≤50and/or epithelial ovarian cancer

      aClose relatives of individuals with the history mentioned in the table are appropriate candidates for genetic counseling. It is optimal to initiate testing in an individual with breast or ovarian cancer prior to testing at-risk relatives.

      bCriteria modified from NCCN (109)


    Continued
    Continued…. AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Personal history of breast cancer and two or more relatives on the same side of the family with breast cancer and/or epithelial ovarian cancer

    • Personal history of epithelial ovarian cancer, diagnosed at any age, particularly if Ashkenazi Jewish

    • Personal history of male breast cancer particularly if at least one first- or second-degree relative with breast cancer and/or epithelial ovarian cancer

    • Relatives of individuals with a deleterious BRCA1/2mutation


    Evolution of breast cancer
    Evolution of Breast Cancer AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    “Cancer of the breast spreads centrifugally.

    It disseminates to bone by way of the lymphatics, not by blood vessels.”

    Halsted, WS. The results of radical operations for the cure of carcinoma of the breast. Ann Surg 1907; 66:1


    Halstedian concept did not apply
    Halstedian concept did not apply AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    More extensive surgical procedures did not reduce risk of distant metastasis

    Identification of small breast cancer by mammography


    National surgical adjuvant breast project
    National Surgical Adjuvant Breast Project AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Radical mastectomy

      vs

    • Simple mastectomy with axillary irradiation

      vs

    • Simple mastectomy with delayed axillary dissection

      Started in 1971, 1665 patients enrolled, 25 year follow up

      No difference in disease free or overall survival


    Breast cancer multifocality holland et al
    Breast Cancer Multifocality AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST Holland et al.

    • Only 37% of cancers are confined to the primary tumor.

    • 20% have additional cancer within 2 cms.

    • 43% have additional cancer beyond 2 cms.

      Holland R, Veling S, Mravunac M, et al. Histologic multifocality of Tis, T1-2 breast carcinomas: implications for clinical trials of breast-conserving treatment. Cancer 1985; 56: 979


    Nsabp b 06
    NSABP B-06 AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Total mastectomy vs lumpectomy vs lumpectomy plus irradiation

    • No significant difference in survival

    • 14.3% recurrence in lumpectomy plus radiation group at 25 years

    • 39.2% recurrence in lumpectomy without radiation group at 25 years


    Conclusion nsabp b 06
    Conclusion NSABP B-06 AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Lumpectomy followed by breast irradiation is the appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.


    Contraindications for breast conserving therapy
    Contraindications for Breast Conserving Therapy AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Absolute:

    • Prior radiation to the breast or chest wall

    • Pregnancy

    • Muticentric disease

    • Diffuse, malignant appearing microcalcifications


    Relative contraindications for bct
    Relative Contraindications for BCT AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • History of collagen vascular disease

    • Very large tumor > 5cms

    • Very large breasts


    Margins
    Margins AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Clear: tumor not touching the ink

    • Close: < 1mm – may be a problem with young or extensive intraductal component


    Algorithm for adjuvant systemic therapy for breast cancer
    ALGORITHM FOR ADJUVANT SYSTEMIC THERAPY FOR BREAST CANCER AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    ER, estrogen receptor; PR, progesterone receptor

    aFormerly HER-2


    Radiation therapy
    Radiation Therapy AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Whole breast with boost to tumor bed standard

    • Accelerated partial breast irradiation

      • Balloon ( Mammosite)

      • Interstitial brachytherapy

      • External beam limited RT

      • Intraoperative limited RT


    Post mastectomy radiation
    Post-mastectomy Radiation AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Early studies showed increased mortality

    • Recent studies show substantial decrease in locoregional recurrence

    • Recent trials show survival benefit 5-8% at > 10 years.


    Indications for post mastectomy radiation
    Indications for Post-mastectomy Radiation AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • T3 or T4 tumors

    • Tumors invading skin or muscle

    • 4 or more pos. axillary nodes

    • (Some recommend for 1-3 nodes, depending)


    Breast reconstruction
    Breast Reconstruction AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Immediate – skin sparing

    • Delayed immediate – skin sparing

    • Delayed


    Skin sparing mastectomy
    Skin Sparing Mastectomy AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    Includes areolar (nipple sparing controversial)

    Excise biopsy incision

    Radiate positive margins


    Axillary biopsy and control
    Axillary Biopsy and Control AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    1. Staging

    • In the absence of distant mets number of positive lymph nodes is the most important prognostic factor.

      2. Regional Control

      In clinically negative axilla, axillary dissection reduces local occurrence from 20% to 3%

      3. Small survival advantage (3-5%)


    Sentinel lymph node
    Sentinel Lymph Node AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Technetium labeled sulfur colloid

    • Isosulfan blue (lymphazurin 1%)

    • Combined – 97% ID’ed; 6% false negative

    • 1% anaphylactic reaction to blue dye


    Locally advanced cancer
    Locally Advanced Cancer AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Large primary tumors (>5cm) especially with pos. nodes

    • Tumors with skin or chest wall involvement

    • Tumors with fixed or matted axillary nodes or ipsilateralsubclavian or supraclavicular lymph nodes

    • Most have been present for months or years but treatment has been delayed


    Inflammatory breast cancer
    Inflammatory Breast Cancer AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Rapid onset and progression over weeks to months

    • Skin often discolored red to purple

    • Skin thickened or peau d’ orange

    • Induration

    • Invasion of dermal lymphatics is a common feature but not required or sufficient for a diagnosis

    • 1-5% of breast cancers


    Neoadjuvant AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST Chemotherapy

    aka

    Preoperative Systemic Therapy

    aka

    Primary Chemotherapy


    Nsabp b 18
    NSABP B-18 AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Started 1988; 1523 pts, 4 cycles AC

    • 80% overall response

    • 13% pathologic complete response

    • No difference in overall survival

    • Only 3% had progression of disease

    • 25% downstaging at axilla

    • 30% of women will downsize to allow conversion from mastectomy to BCS


    Indications
    Indications AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • To downsize women with large tumors that cannot undergo BCS with good cosmetic result – 30% of women will downsize.

    • Early initiation of systemic treatment

    • In vivo assessment of response, good biological model

    • Less radical surgery needed


    Pre operative endocrine therapy
    Pre-operative Endocrine Therapy AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST

    • Best for large low grade ER pos. tumors in post menopausal women

    • Response times 3 months or longer

    • Greater response with aromatase inhibitors compared with tamoxifen

    • Under-utilized in the US


    Tulane surgery: AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST “ tough as the marines except the marines get to eat”


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