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Sentinel Lymph Node Biopsy and Pregancy

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Sentinel lymph node biopsy (SLNB):
    • Is the standard of care in patients with early stage, clinically node negative breast cancer
  • Compared to axillary lymph node dissection (ALND):
    • SLNB has lower morbidity, including:
      • A lower risk of musculoskeletal limitations and lymphedema
    • In general, SLNB can be performed with the use of blue dye, technetium-99 (99mTc), or dual agents
  • The role of SLNB in pregnancy:
    • Is not clearly defined:
      • Recently updated American Society of Clinical Oncology (ASCO) Guidelines:
        • Upholds its prior recommendation that SLNB should not be performed in pregnancy:
          • The strength of the recommendation, however, is described by the ASCO expert panel to be “weak,” as it is based on ”informal consensus” rather than quality evidence
    • Several retrospective studies have described the safety of SLNB during pregnancy:
      • The majority of patients in these studies underwent SLNB with 99mTc alone; however, methylene blue dye was used in some patients
      • One recent retrospective review reported on 145 women with clinical node-negative disease who underwent SLNB during pregnancy:
        • The mapping agents utilized were 99mTc alone (66%), methylene blue dye alone (9.7%), dual agents (10.3%), and the remainder was unknown
        • Sentinel lymph nodes were identified in 99.3% of patients, with excellent gestational outcomes
        • No neonatal adverse events related to the SLNB procedure were reported
  • Models of fetal radiation exposure:
    • Have demonstrated that the use of 99mTc for SLNB leads to a negligible dose to the fetus of 0.014 mGy or less:
      • Whereas risk of fetal malformation is associated with levels greater than 100 mGy
    • Lower doses of exposure can be achieved using a 1-day protocol rather than a 2-day protocol
  • The use of lymphazurin dye:
    • Is not recommended due to the 1 to 2% risk of anaphylaxis
  • Historically, the use of direct intra-amniotic injection of methylene blue dye for identification of ruptured membranes led to significant neonatal complications:
    • Recent pharmacokinetic data indicate that the absorption of methylene blue dye used during SLNB is minimal
    • Although the use of methylene blue dye for SLNB has been described:
      • The data are limited in comparison to that of 99mTc
  • Thus, with respect to axillary staging:
    • The risks and benefits of ALND vs. SLNB must be discussed with the patient prior to surgery
  • References
    • Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220(3):391-398.
    • Lyman GH, Somerfield MR, Bosserman LD, Perkins CL, Weaver DL, Giuliano AE. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.J Clin Oncol.2017;35(5):561-564.
    • Han SN, Amant F, Cardonick EH, et al. Axillary staging for breast cancer during pregnancy: feasibility and safety of sentinel lymph node biopsy. Breast Cancer Res Treat. 2018;168(2):551-557.
    • Gropper AB, Calvillo KZ, Dominici L, et al. Sentinel lymph node biopsy in pregnant women with breast cancer. Ann Surg Oncol. 2014;21(8):2506-2511.
    • Gentilini O, Cremonesi M, Toesca A et al. Sentinel lymph node biopsy in pregnant patients with breast cancer. Eur J Nucl Med Mol Imaging. 2010;37(1):78-83.
    • Pandit-Taskar N, Dauer LT, Montgomery L et al. Organ and fetal absorbed dose estimates from 99mTc-sulfur colloid lymphoscintigraphy and sentinel node localization in breast cancer patients. J Nucl Med. 2006;47(7):1202-1208.
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Red Flags for Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Koo and colleagues collected and analyzed data from more than 2300 women with symptomatic breast cancer diagnosed in the United Kingdom
  • A total of 56 presenting symptoms were reported
  • Among them, breast lump was the most common (83%), followed by nipple abnormalities (7%), breast pain (6%), and breast skin abnormalities (2%)
  • More rarely, patients presented with non-breast symptoms suggestive of metastatic disease, such as back pain (1%) and weight loss (0.3%)
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High-Risk Assessment of Early Breast Cancer V

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • In 2022, both the US Food and Drug Administration and the European Union approved adjuvant olaparib, a PARP inhibitor, for the treatment of patients with deleterious or suspected deleterious germline BRCA mutation (gBRCAm) and a diagnosis of HER2-negative, high-risk, early-stage breast cancer treated with neoadjuvant or adjuvant chemotherapy
  • A diagnostic companion test for germline BRCA status is needed to select patients for this treatment
  • Olaparib was approved on the basis of findings of the OlympiA trial, a phase 3 trial in which patients carrying a germline BRCA alteration and a diagnosis of HER2-negative, high-risk, early-stage breast cancer were randomly assigned to receive 1 year of olaparib or placebo after (neo)adjuvant chemotherapy
  • A statistically significant improvement in invasive disease-free survival and overall survival was demonstrated in patients in the olaparib arm compared with the placebo arm
  • The safety profile of olaparib was consistent with previously reported side effects
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High-Risk Assessment of Early Breast Cancer IV

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • As with other early breast cancers (eg, hormone-positive or triple-negative), risk for recurrence of a HER2-positive tumor is generally dependent on tumor size, presence of positive axillary lymph nodes, tumor grade, and other histologic and patient factors
  • Before the development of effective anti-HER2 therapies, such as trastuzumab, novel anti-HER2 tyrosine kinase inhibitors (TKIs), or antibody drug conjugates (ADCs) HER2 positivity was associated with poor prognosis
  • The degree of HER2 positivity (ie, IHC 2+/FISH amplified vs IHC 3+) is not correlated with recurrence risk, although it may be associated with greater responsiveness to anti-HER2–targeted therapies
  • Patients with early-stage, HER2-positive tumors with clinically positive lymph nodes are candidates for neoadjuvant systemic treatment with chemotherapy and pertuzumab plus trastuzumab
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High-Risk Assessment of Early Breast Cancer III

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • According to the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO), decisions about adding chemotherapy to adjuvant endocrine therapy are individualized on the basis of patient and disease factors, including results of genomic assays
  • Most cases of small ER-positive, PR-positive, HER2-negative, node-negative breast cancer have a good prognosis with endocrine therapy alone and do not require adjuvant chemotherapy
  • By contrast, tumors that are high-grade, with higher measures of proliferation and lower levels of ER/PR expression, tend to be less sensitive to endocrine treatment and are more likely to benefit from adjuvant chemotherapy
  • Although assessment of response to neoadjuvant endocrine therapy or chemotherapy is used in the setting of locally advanced breast cancer, particularly when the size and/or location of the tumor preclude breast-conserving surgery, patients with very small, early, HER2-negative, hormone-positive cancers are generally treated with surgery first, followed by radiation therapy and consideration of adjuvant therapy with an endocrine regimen, chemotherapy, or both
  • Ki67 is an indirect measure of cell proliferation
  • Although a high Ki67 score is often considered a marker for poorer prognosis in early breast cancer, it cannot predict the benefit of chemotherapy as a single measure
  • Recently, the International Ki67 in Breast Cancer Working Group concluded that Ki67 has limited value for treatment decisions due to questionable analytical limitations
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Red Flags for Breast Cancer IV

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Inflammatory breast cancer is an aggressive type of breast cancer that requires urgent workup and treatment
  • Detection by mammography is limited due to low sensitivity; hence, diagnosis of inflammatory breast cancer is based on clinical factors and defined as a rapid onset of breast erythema, edema and/or peau d’orange, and/or warm breast, with or without an underlying palpable mass
  • Immediate referral to medical and surgical oncologists is essential when inflammatory breast cancer is suspected
  • Because it is not uncommon for women with inflammatory breast cancer to have metastatic disease at the time of diagnosis, inflammatory breast cancer should be staged with full-body imaging, such as PET-CT or CT of the chest, abdomen, and pelvis, plus a bone scan
  • When the presence of metastatic disease is ruled out, inflammatory breast cancer is treated with chemotherapy upfront (ie, neoadjuvant), before surgery
  • Axillary adenopathy may or may not be present
  • Crusting and retraction of nipples may or may not occur
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High-Risk Assessment of Early Breast Cancer II

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Although women with at least one first-degree relative with a history of breast cancer have a two- to three fold excess risk of developing the disease, only 5% to 10% have an identifiable hereditary predisposition
  • On average, women with a germline BRCA1 mutation have a 72% risk of developing breast cancer by age 80 years
  • For those with a germline BRCA2 mutation, the risk is 69%
  • The highest rates of BRCA1 mutations occur among Ashkenazi Jewish women
  • Because of the high lifetime risk for breast cancer in germline BRCA mutation carriers, both American and European guidelines recommend considering prophylactic surgery, such as double mastectomy
  • Other women at high risk of developing breast cancer because of a hereditary predisposition may opt for frequent imaging
  • Breast cancers that develop in germline BRCA1 mutation carriers are more likely to be high-grade, as well as triple-negative or basal-like subtype, whereas those with BRCA2 mutations are more likely to develop a high-grade, hormone receptor–positive/HER2-negative tumor
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Breast Cancer Subtypes

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • One of the most important factors to be considered with breast cancer diagnosis is breast cancer subtype
  • There are three major breast cancer subtypes: luminal-like, HER2-positive, and triple-negative, which are identified by the expression of hormone receptors and HER2 by breast cancer cells
  • Of note, these subtypes have different biologic features, prognosis, and response to treatment
  • Although all breast cancers may recur despite treatment, those defined as triple-negative breast cancer (TNBC), which lack specific targets for effective treatments, are considered high risk
  • Hence, up to 40% of early-stage breast cancer patients will experience recurrence after standard treatment
  • Tumors expressing hormone receptors (ie, estrogen and progesterone receptors) are defined as luminal-like, are typically less aggressive, and have a good prognosis
  • HER2-positive breast tumors are biologically aggressive tumors, but the outcome has dramatically improved with anti-HER2 targeted therapies
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Adjuvant Endocrine Therapy for Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Several trials showed that extended adjuvant endocrine therapy beyond 5 years provides additional benefit in terms of reduction of disease recurrence
  • According to ASCO guidelines, all patients with node-positive disease should be offered 10 years of adjuvant ET
  • Guidelines from the European Society for Medical Oncology (ESMO) also note that 10 years of treatment is advantageous. Moreover, women with node-negative breast cancer may be offered extended adjuvant endocrine therapy for up to 10 years, on the basis of considerations of recurrence risk using established prognostic factors
  • Conversely, women with low-risk, node-negative tumors should notroutinely be offered extended therapy because the absolute reduction of recurrence risk is likely to be small in this category of patients
  • The ESMO notes that extended therapy should not be offered to those with a very low risk of relapse
  • Similarly, 5 years of ovarian function suppression with either tamoxifen or an aromatase inhibitor provides an additional benefit for this patient population. However, there is no evidence that continuing ovarian function suppression alone beyond 5 years provides additional benefit

Red Flags for Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Although most breast cancers do not present with any symptom and are diagnosed through screening mammograms, breast cancer may present with different signs and symptoms, including breast lumps, nipple inversion and discharge, and peau d’orange
  • Signs in palpable lumps that should raise concern include focal nodularity, hardness, irregularity, and asymmetry with the other breast
#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #Miami #Mexico #BreastCancer #MountSinaiMedicalCenter #MSMC #Doctor