Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

👉 The rationale for performing sentinel lymph node biopsy (SLNB) is to have nodal staging in the event invasive carcinoma is identified pathologically in the breast that was removed prophylactically

👉 Multiple studies have reported that the chance of finding invasive disease in the surgical specimen with prophylactic mastectomy is less than 3%

👉 In a large series from the MD Anderson Cancer Center that included 436 prophylactic mastectomies, cancer was identified in 22 (5%) cases

👉 Of these, the majority of patients (14) had ductal carcinoma in situ

👉 Only eight patients (1.8%) had invasive cancer, with a mean tumor size of 5 mm

👉 The study included 23 patients with BRCA mutations, and no invasive cancers were identified in these cases

👉 Significantly increased risk of invasive cancer in the prophylactic mastectomy was seen in postmenopausal patients (3.7%; p=0.007), patients age greater than 60 years (7.5%; p=0.008), and patients with invasive lobular carcinoma (9.7%; p0.0002) or lobular carcinoma in situ (7.7%; p=0.008).

👉 A decision-analytic model was created by the same group to compare the risk / benefit ratio of routine SLNB for all prophylactic mastectomies compared to omitting SLNB and performing ALND only when invasive cancer is found in the breast

👉 The pertinent literature was reviewed to determine the chance of finding invasive cancer in a prophylactic mastectomy specimen and to estimate the chance of complications (lymphedema, paresthesias, decreased range of shoulder motion) with SNLB and ALND

👉 At a rate of finding invasive cancer of 1.9%, 73 SLNBs were required to avoid 1 ALND

👉 After reviewing the literature, the complication rate was estimated at 7% for SLNBs and 31% for ALND

👉 In one model scenario, the probability of complications per breast cancer detected was 9-fold greater with the SLNBs strategy than with the directed ALND strategy

👉 This model supported the decision to forego SLNB in most patients undergoing prophylactic mastectomy, given the large number of procedures required to benefit one patient

👉Rodrigo Arrangoiz MS, MD, FACS, FSSO cirujano oncólogo y cirujano de mamá  en Mount Sinai Medical Center en Miami:

• Es experto en el manejo del cáncer de mama

👉Es miembro de la American Society of Breast Surgeons:

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

#Arrangoiz

#Surgeon

#Cirujano

#SurgicalOncologist

#CirujanoOncologo

#BreastSurgeon

#CirujanodeMama

#CancerSurgeon

#CirujanodeCancer

• The standard of care with respect to surgical management of early stage breast cancer with a clinically negative axilla:
  • Is to undergo axillary staging with sentinel lymph node mapping and biopsy (SLNM / SLNB)
• In patients who are clinically node negative undergoing lumpectomy with SLNB:
  • A completion axillary lymph node dissection (ALND) is not required if one or two lymph nodes are positive:
    • These patients should go on to receive adjuvant therapy
  • Omission of ALND:
    • Does not lead to a difference in 10-year locoregional recurrence or overall survival
• There is, however, a role for omission of axillary staging in elderly women:
  • Who are clinically node negative with ER+ tumors:
    • Particularly if co-morbidities are present
• The Cancer and Leukemia Group B (CALBG) 9343 study:
  • Evaluated women ≥ 70 years of age who underwent lumpectomy for clinical T1, N0, ER+ breast cancer +/- adjuvant radiation (RT):
    • With tamoxifen (Tam) recommended for all patients
  • Of the 636 participants:
    • 404 (64%) did not undergo any initial axillary surgery
    • At 12-year follow-up:
      • There were no axillary recurrences among women who underwent initial axillary dissection
      • Among those who did not undergo axillary dissection:
        • There were no axillary recurrences in the Tam + RT group
        • Six of 200 in the Tam only group (3%) had axillary recurrences
• The International Breast Cancer Study Group Trial 10-93:
  • Evaluated 473 patients with early stage breast cancer who were clinically node negative
  • Patients had a mean age of 74
  • The majority of patients were ER+
  • Patients were randomized to breast surgery +/- axillary dissection followed by endocrine therapy
  • Overall, 2% of patients had an axillary recurrence:
    • 1% of those with axillary surgery vs. 3% in patients without axillary surgery:
      • With no difference in disease-free and overall survival
• Results from these and other studies recently led the Society of Surgical Oncology to release the Choosing WiselyÒ guidelines:
  • Recommending against routine use of SLNB in clinically node-negative women ≥70 years of age with hormone positive cancer
  • Hormonal therapy:
    • Is typically recommended for patients with hormone receptor positive disease
  • Omission of SLNB in clinically node-negative women ≥70 years of age treated with hormonal therapy:
    • Does not result in a significantly increased rate of locoregional recurrence and does not impact breast cancer mortality:
      • Thus, although axillary staging with SLNB continues to be the standard of care, omission of axillary staging can be considered in some patients ≥70 years of age with early stage, clinically node-negative, hormone receptor positive breast cancer
• References:
  • Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg. 2016;264(3):413-420.
  • Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017;318(10):918-926.
  • Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31(19):2382-2387.
  • International Breast Cancer Study Group: Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93. J Clin Oncol.2006;24(3):337-344.
  • Society of Surgical Oncology. Five things physicians and patients should question. Choosing Wisely website. Released July 12, 2016; updated June 20, 2019. http://www.choosingwisely.org/societies/society-of-surgical-oncology. Accessed August 25, 2019.

• Improvements in adjuvant therapy for breast cancer:
  • Have allowed surgeons to perform less aggressive surgical procedures safely
• Axillary staging in women with hormone-positive (HR+) breast cancer (BC) and clinically negative lymph nodes has evolved from upfront axillary lymph node dissection (ALND) to sentinel lymph node mapping an biopsy (SLNM / SLNB):
  • Landmark trial NSABP-32:
    • Demonstrated no difference in survival or locoregional control in patients who received ALND compared to SLNB:
      • Thereby propelling SLNM / SLNB as the gold standard for axillary evaluation in patients with negative clinical axillae
• Although more slowly adopted, de-escalating axillary surgery by omitting SLMN / SLNB:
  • Has been shown to be safe in selected patient populations such as:
    • Older women with early-stage HR+ tumors
• In Western countries:
  • Nearly a third of breast cancers (BCs) occur in patients over 65:
    • With the greatest incidence in women aged 75 to 79
• Given the central role of surgery:
  • The question arises as to whether the surgical evaluation of the axilla is necessary for older patients with early BC and clinically negative axillary nodes
• The American Board of Internal Medicine Foundation:
  • Launched a national initiative called Choosing Wisely to prompt provider discussion about the appropriate use of tests, treatments, and procedures based on evidence-driven medicine
  • In conjunction with the Society of Surgical Oncology in 2016:
    • Recommendations were released:
      • The first recommendation stated “Don’t routinely use sentinel node biopsy in clinically node-negative women ≥70 years of age with early-stage hormone receptor-positive, HER2 negative invasive breast cancer”:
      • This recommendation was based on several prospective trials highlighting that SLNB had no impact on locoregional recurrence or breast-cancer-specific mortality (BCSS)
• One such trial was conducted by Martelli et al evaluating the long-term safety of no axillary surgery for patients > 70 years old with operable BC and negative clinical axillae who received adjuvant endocrine therapy:
  • This study found that axillary surgery did not increase overall survival (OS) or BCSS over 5 years
  • The cumulative 15-year incidence of axillary disease:
    • Remained low at 5.8% and 3.7% for T1 patients who received ALND compared to those who did not
  • Martelli et al concluded there was:
    • No benefit to axillary surgery for older patients with node-negative early BC who received BCS with adjuvant endocrine therapy
• Similarly, Chung et al evaluated the safety of SLNB omission in women >70 years old with T1 to T2 tumors:
  • The 5-year OS was 70%:
    • Whereas BCSS was 96%:
      • Ischemic heart disease was the most common cause of death
  • The authors also found that adjuvant therapy was less likely to be offered regardless of nodal status, indicating that nodal status did not influence care:
    • As patients were more likely to die from causes other than BC
• The IBCSG 10-93 trial:
  • Assessed whether omitting axillary surgery in older people would improve quality of life (QOL) with equivalent disease-free survival (DFS) and OS:
    • A total of 473 women received primary breast surgery with adjuvant tamoxifen and were randomly assigned to receive or omit axillary staging
    • Adverse QOL effects from axillary surgery were evident early in the postoperative period but dissipated 6 to 12 months after surgery
    • At the 6-year follow-up:
      • There was no difference in DFS or OS
    • The investigators concluded that the omission of axillary surgery corresponded with improved early QOL without differences in DFS or OS
• CALGB 9343:
  • Which addressed the need for adjuvant radiation after a lumpectomy in early-stage HR+ BC in older people, included a small subset of patients who received no axillary surgery or radiation:
    • In this patient cohort, only 3% developed ipsilateral axillary recurrence compared to no recurrences in patients who received radiation without axillary staging
    • Due to low axillary recurrence among those who had omitted nodal surgery and radiotherapy:
      • Authors surmised SLNB might be safely omitted in this population
• Application of Choosing Wisely in clinical practice:
  • After releasing the Choosing Wisely recommendation, Welsh et al sought to develop a risk stratification model to facilitate guideline adoption for patients at low risk for nodal positivity
  • Using the National Cancer Database data from 2010 to 2013, a total of 71,834 patients met the criteria for SLNB omission
  • The pathologic nodal positivity rate for patients with axillary staging was 15.3%
  • Welsh et al classified low-risk patients as those with:
    • Grade 1 less than 2 cm tumors or grade 2 less than 1 cm tumors:
      • Translating to a nodal positivity rate of 7.8% compared to 22.3% among patients who did not meet low-risk criteria
    • The authors concluded that SLNB might be safely omitted in older patients with:
      • Grade 1 cT1mi to T1c HR+ tumors
      • Grade 2 cT1mi to T1b HR+ tumors

• Moorman explored the utility of a nomogram to aid decision-making for SLNB omission:
  • Presenting a model with an excellent predictive value that can select one-third of patients in whom SLNB is deemed unnecessary because of a less than 5% chance of nodal involvement
• Similar nomograms have been adopted by MSKCC and the Mayo Clinic to predict the likelihood of nodal positivity
• Additionally, the ongoing prospective Sentinel Node Vs Observation After Axillary Ultra-souND trial:
  • Examines the safety of SNLB omission in patients of any age with T1 tumors and clinically, radiographically negative axillae without prior systemic treatment:
    • This trial will clarify the safety of SNLB omission in patients with small tumors while examining the effects on adjuvant treatment and quality of life
• Adherence to Choosing Wisely
  • Several investigators have demonstrated the slow implementation of Choosing Wisely campaign in clinical practice
  • For example, Wang et al examined 4 low-value BC operations identified through the Choosing Wisely campaign before and after evidence demonstrated that each procedure was unnecessary:
    • The retrospective cohort study using the National Cancer Database registry, which included 1,500 facilities across the United States, examined a total of 920,256 women with a median age of 63 years diagnosed with BC between 2004 and 2016 and identified 4 low-value BC operation cohorts: ALND, lumpectomy margin reoperation, contralateral prophylactic mastectomy, and SLNB
    • Although ALND and margin re-excision surgeries decreased during the study period, rates of contralateral prophylactic mastectomy and SLNB in older women increased
    • Academic research programs and high-volume facilities demonstrated the greatest reduction in use, indicating that facility-level characteristics were associated with the use of low-value BC operations
  • This was further corroborated by Armani et al, whose survey showed that although academic centers were more likely to practice according to national guidelines, adherence overall was low
  • Tonneson et al identified a group of women at low risk of nodal positivity where SLNB may be omitted (grade 1, cT1mi-T1c, or grade 2, cT1mi-T1b) and evaluated the impact of SLNB omission by performing a retrospective chart review of women aged ≥70 years with HR+ node-negative BC at the Mayo Clinic between 2010 and 2020 and compared SLNB use before (2010–2016) and after (2017–2020) the Choosing Wisely guideline release according to clinical risk and the association with adjuvant therapy:
    • This group found that the SLNB surgery rate significantly decreased from 90.6% (2010–2016) to 62.8% in 2020 (P < .001) and that this was driven by BCS with SLNB rates of 88.2% (2010–2016) and 46.7% in 2020
• In conclusion, the safety and efficacy of the omission of SLNB with ER+ BC in older people continues to be studied:
  • Choosing Wisely states that routine SLNB should not be performed in this population, acknowledging that a subset of patients is low risk and may be spared the morbidity of axillary staging
• Ongoing research continues to identify these low-risk populations while improving adherence to Choosing Wisely guidelines to prevent overtreatment in the rest of this cohort

• 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)
    • Dual agents
• The role of SLNB in pregnancy:
  • Is not clearly defined:
    • 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.

• Estrogen receptor positive (ER+) tumors:
  • Can be very sensitive to endocrine therapy:
    • Which may allow some patients to safely avoid chemotherapy
    • However, the presence of ER receptors on immunohistochemistry:
      • Does not necessarily mean that the tumor’s growth is being driven by ER-related pathways
• Additionally, other molecular features may influence the tumor cells’ sensitivity to hormonal therapy
• The development of predictive molecular assays:
  • Has been a major advancement in the field
• The assay (Oncotype Dx) measures mRNA expression of 21 genes:
  • Using reverse transcriptase-polymerase chain reaction techniques
  • It can be performed on formalin-fixed paraffin-embedded tumor specimens obtained by core biopsy or surgery
  • It has been validated in:
    • ER+, node-negative women who have not received any prior therapy
  • This assay is more reliable in predicting cancer recurrence than such clinical parameters as size, hormone receptor status, nuclear grade, or Ki-67 alone
• The assay measures downstream ER-regulated genes:
  • To assess the functionality of the ER receptor
• Patients with low scores (< 18):
  • Are considered at low risk for disease recurrence and may not receive any benefit from adjuvant chemotherapy
  • These patients are now treated with hormonal therapy alone without cytotoxic chemotherapy
  • In fact, the published subset analysis of the prospective validation of the 21-gene expression assay in breast cancer:
    • Confirmed that 98.7% of women with 21-gene signature scores of less than 10 managed with endocrine therapy alone had no evidence of local, regional, or distant recurrence at 5 years
• Patients with a high score (> 31):
  • Have been shown to gain a large benefit from the addition of chemotherapy
• While the assay is not performed on HER2-overexpressing tumors:
  • It does measure HER2 and other proliferative genes
• It was only validated for node-negative patients:
  • The RxPONDER (SWOG 1007) trial:
    • Evaluated women with 1 to 3 positive lymph nodes and an 21-gene signature score of less than 25
    • These patients were randomized to receive chemotherapy and endocrine therapy to endocrine therapy alone
    • Results:
      • Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease–free survival and distant relapse–free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy
• References:
  • Paik S. Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen. Oncologist. 2007;12(6):631-635.
  • Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817-2826.
  • Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-3734.
  • Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. New Engl J Med. 2015;373(21):2005-2014.

• Triple-negative breast cancer:
  • Is more responsive to preoperative chemotherapy:
    • Compared to ER + / PR+, HER2neu negative breast cancer
  • Pathologic complete response:
    • Is seen in approximately 30% to 40% of patients undergoing treatment with a third-generation regimen:
      • A pathologic complete response is highly prognostic in this subset
• While ER negative breast cancers have a lower propensity for regional nodal metastasis compared to ER+ tumors:
  • The difference is relatively small (2% to 5%):
    • Therefore, nodal staging is still a standard practice recommendation
• The Choosing Wisely guideline:
  • For omission of routine use of sentinel node biopsy in clinically node-negative women ≥ 70 years of age:
    • Applies to hormone receptor positive breast cancer
• Sentinel node biopsy:
  • May be successfully performed after neoadjuvant chemotherapy
• References:
  • Cortazar P, Zhang L, Untch M, et al. Pathologic complete response and long term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-172.
  • Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25(28):4414-4422.
  • von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796-1804.
  • Viale G, Zurrida S, Maiorano E, et al. Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution. Cancer. 2005;103(3):492-500.
  • Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31(19):2382-2387.
  • Five things physicians and patients should question. June 20, 2019. Choosing Wisely: Society of Surgical Oncology website. http://www.choosingwisely.org/societies/society-of-surgical-oncology/. Accessed September 21, 2019.
    
    

• The biology and outcomes of bilateral breast cancer:
  • Continue to be of interest, but the recommendations for optimal treatment are sometimes difficult
• Synchronous and metachronous bilateral breast cancers:
  • Range from 1% to 20% of patients with breast cancer
• Improvements in screening and the increased use of MRI:
  • Often diagnose more early-stage synchronous bilateral cancer
• Women with a history of breast cancer:
  • Are at increased risk of a metachronous cancer:
    • Improvements in survival necessitate continued screening for future contralateral cancers
  • Historically, controversy existed as to whether all bilateral breast cancers were harbingers of an underlying genetic abnormality with worse recurrence rates and survival:
    • However, most bilateral breast cancers are not caused by germline mutations such as BRCA:
      • But may be associated with environmental factors or prolonged hormonal exposure
• Retrospective studies evaluating the outcomes of synchronous bilateral breast cancer are limited by small cohort sizes, differing definitions, and non-matched unilateral patients as controls
• Most retrospective studies show no differences in local recurrence or survival for bilateral breast cancers:
  • Making bilateral breast-conserving treatment:
    • A safe option for early-stage synchronous cancers
• Irvine et al:
  • Showed that survival is based on the more advanced cancer and that the secondary cancer does not affect overall prognosis
  • This study was able to match patients with comparable unilateral breast cancer patients and showed similar outcomes
• Newman et al:
  • Also found that patients with bilateral cancer were more likely to have multicentric disease and a family history of breast cancer:
    • But there was no difference in 5-year disease-free survival
• However, another study that did not match patients also found no differences in local control or overall survival among unilateral, metachronous, and synchronous breast cancer patients on multivariate analysis:
  • But found a greater risk of distant metastasis in the 47 patients with synchronous disease
• Advances in CT scan-based simulation for bilateral breast radiation:
  • Have made bilateral radiation feasible for early-stage breast cancers
• Advanced cancers with extensive nodal involvement:
  • Might pose a problem with overlapping internal mammary fields
• Understanding the interplay among competing risk factors,including a patient’s personal history, family history, the presence of a BRCA mutation, life expectancy, and tumor biology:
  • Offers greater insight to managing this increasingly common entity
• References:
  • Beinart G, Gonzalez-Angulo AM, Broglio K, et al. Clinical course of 771 patients with bilateral breast cancer: characteristics associated with overall and recurrence-free survival. Clin Breast Cancer. 2007;7(11):867-874.
  • Heron DE, Komarnicky LT, Hyslop T, Schwartz GF, Mansfield CM. Bilateral breast carcinoma: risk factors and outcomes for patients with synchronous and metachronous disease. Cancer. 2000;88(12):2739-2750.
  • Intra M, Rotmensz N, Viale G, et al. Clinicopathologic characteristics of 143 patients with synchronous bilateral invasive breast carcinomas treated in a single institution. Cancer. 2004;101(5):905-912.
  • Irvine T, Allen DS, Gillett C, Hamed H, Fentiman IS. Prognosis of synchronous bilateral breast cancer. Br J Surg. 2009;96(4):376-380.
  • Newman LA, Sahin AA, Cunningham JE, et al. A case-control study of unilateral and bilateral breast carcinoma patients. Cancer. 2001;91(10):1845-1853. Erratum in: Cancer. 2002;94(4):1191.

• Metaplastic carcinoma of the breast (MCB):
  • Tends to present in patients age 60 years and older:
    • Is rare in young or premenopausal women
• Compared to invasive ductal carcinoma (IDC):
  • It has been shown to present in a higher proportion of:
    • African Americans and Hispanics
• Metaplastic breast cancer (MBC):
  • Is more likely to be high grade but axillary node negative at presentation
  • The mean tumor size is about 4 cm
• Patients with this diagnosis are also more likely to:
  • Receive chemotherapy and undergo mastectomy
• Recurrence tends to be locoregional or pulmonary and is associated with a high mortality rate
• Future directions may include immunotherapies, as MBC has a unique histology demonstrating increased PDL-1:
  • Which may make it a good candidate for targeted therapy
• More research is needed on this unique tumor phenotype
  • References
    • Pezzi CM, Patel-Parekh L, Cole K, Frank J, Klimberg VS, Bland K. Characteristics and treatment of metaplastic breast cancer: analysis of 892 cases from the National Cancer Data Base. Ann Surg Oncol. 2006;14(1):166-173.
    • Schwartz T, Mogal H, Papageorgiou C, Veerapong J, Hsueh EC. Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies. Exp Hematol Oncol. 2013;(1)2:31.
    • Haque W, Teh BS. Current practice and future directions for metaplastic breast cancer. Ann Surg Oncol. 2018;25(Suppl 3):630-631.

• The mammogram shows extremely dense breast tissue without other abnormality

• Because no particle movement could be identified, one cannot be certain the mass is not solid:
  • If solid, the sonographic mass has none of the 10 signs of malignancy, but it also does not meet any of the 3 strict benign criteria:
    • 10 signs of malignancy on ultrasound:
      • Shadowing
      • Hypoechoic ecotexutre
      • Spiculation
      • Angular Margins
      • Thick echogenic halo
      • Microlobulation
      • Taller than wider
      • Duct Extension
      • Branching pattern
      • Calcifications
  • The three benign findings defined by Stavros are:
    • A purely hyperechoic lesion with no hypoechoic area larger than a normal duct or lobule
    • Elliptical, wider than tall, well-circumscribed and thin echogenic capsule
    • Gently lobulated, wider than tall, well-circumscribed and thin echogenic capsule
• The ultrasound shows a round lesion that is neither elliptical nor gently lobulated, so even if a thin echogenic capsule could be identified, none of the 3 defined benign criteria are met:
  • When there is a thin echogenic capsule in a solid lesion that does not meet the other criteria:
  • There is a 14% chance of malignancy:
    • Therefore, further evaluation is necessary
• Complicated cysts (Image):
  • Differ from simple cysts:
    • Only with regard to internal echoes
  • Complicated cysts are circumscribed and show posterior acoustical enhancement:
    • But are not anechoic
  • They are old cysts that have gradually lost fluid through absorption:
    • Leaving behind proteinaceous fluid, cholesterol crystals, blood, or other substances:
      • That cause low-level internal echoes
    • They can sometimes be difficult to distinguish from hypoechoic solid lesions
    • If one can demonstrate swirling of particles within the mass either by “bouncing” the transducer against the lesion or increasing the power of the beam:
      • The diagnosis of a cystic lesion can be made
    • If there is no movement of particles:
    • A solid mass cannot be excluded
    • Although the lesion shown above would be considered BIRADS 3 by many radiologists, and 6-month follow-up would perhaps be recommended, that approach might cause unnecessary anxiety:
      • There would also be the possibility of diagnostic delay if the lesion turned out to be a well-circumscribed cancer
    • For these reasons, the best approach is to aspirate the lesion and try to evacuate the fluid:
      • Sometimes the “fluid” is the consistency of toothpaste and requires a 16- or even 14-gauge needle to evacuate it:
        • If nothing is obtained with a large bore needle, core needle biopsy is indicated

• A “complex” cyst:
  • Has both cystic and solid components (Images)
  • The solid component may take the form of:
    • An intracystic mass or a thickened septum with a convex component
  • Biopsy is indicated to establish the diagnosis
  • If the lesion is large enough, biopsy can usually be obtained with a core device without vacuum assistance
  • If the lesion is predominately cystic with a thickened, convex septum:
    • Percutaneous vacuum-assisted or surgical excision may be required because the lesion may not be visible after initial core needle targeting, resulting in incomplete sampling
  • Vacuum-assisted sampling is usually adequate to establish a diagnosis and plan surgical therapy, if needed
  • On the other hand, surgical excision of either of these complex cysts would give the pathologist the advantage of examining the entire specimen intact
• References
  • D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA. ACR BI-RADS^® Atlas: Breast Imaging Reporting and Data System, 5^th ed. Reston, VA: American College of Radiology; 2013.
  • Berg WA, Sechtin AC, Marques H, Zhang Z. Cystic breast masses and the ACRIN 666 experience. Radiol Clin North Am. 2010;48(5):931-987.
  • Stavros AT. Sonographic evaluation of breast cysts. In: Stavros AT. Breast Ultrasound. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:276-350.

• A 42-year-old woman with no family history of breast cancer or previous breast problems presents for evaluation of a palpable mass she noticed 1 week ago:
  • She does not perform regular self-examination and is not certain the lump is new
  • A screening mammogram performed 3 months ago (Images) is unchanged from 1 year ago
  • Ultrasound imaging of the palpable lesion is shown in Image 2:
    • You alternately compress and relax the transducer and also increase the power of the beam, but you cannot demonstrate movement of particles within the mass.
      • What would you recommend?

• The mammogram shows extremely dense breast tissue without other abnormality
  • Palpable breast masses might be present in patients with a negative mammogram:
    • This lesions can be obscured by the dense breast tissue
  • Repeating a mammogram is unlikely to show the lesion
• As is true for most breast lesions:
  • Excision should not be the initial management:
    • A diagnosis can be obtained with a needle

• No particle movement could be identified on ultrasound of the breast nodule:
  • One cannot be certain the mass is not solid:
    • If solid, the sonographic mass has none of the 10 signs of malignancy, but it also does not meet any of the 3 strict benign criteria:
      • It is round and neither elliptical nor gently lobulated, so even if a thin echogenic capsule could be identified:
        • None of the three defined benign criteria are met
      • When there is a thin echogenic capsule in a solid lesion that does not meet the other criteria:
        • There is a 14% chance of malignancy:
          • Therefore, further evaluation is necessary
• Complicated cysts (Image) differ from simple cysts:
  • Only with regard to internal echoes
• Complicated cysts are:
  • Circumscribed and show posterior acoustical enhancement:
    • But are not anechoic
  • They are old cysts:
    • That have gradually lost fluid through absorption:
      • Leaving behind proteinaceous fluid, cholesterol crystals, blood, or other substances:
        • That cause low-level internal echoes
  • They can sometimes be difficult to distinguish from hypoechoic solid lesions
  • If one can demonstrate swirling of particles within the mass:
    • Either by “bouncing” the transducer against the lesion or increasing the power of the beam:
      • The diagnosis of a cystic lesion can be made
  • If there is no movement of particles:
    • A solid mass cannot be excluded
  • Although the lesion shown above would be considered BIRADS III by many radiologists, and 6-month follow-up would perhaps be recommended:
    • That approach might cause unnecessary anxiety:
      • There would also be the possibility of diagnostic delay if the lesion turned out to be a well-circumscribed cancer:
        • For these reasons, the best approach is to aspirate the lesion and try to evacuate the fluid
        • Sometimes the “fluid” is the consistency of toothpaste and requires a 16- or even 14-gauge needle to evacuate it
        • If nothing is obtained with a large bore needle:
          • Core needle biopsy is indicated.
• A “complex” cyst has both cystic and solid components (Images)

• The solid component may take the form of an intracystic mass (Image) or a thickened septum with a convex component
• Biopsy is indicated to establish the diagnosis
• If the lesion is large enough (Image), biopsy can usually be obtained with a core device without vacuum assistance
• If the lesion is predominately cystic with a thickened, convex septum, percutaneous vacuum-assisted or surgical excision may be required because the lesion may not be visible after initial core needle targeting, resulting in incomplete sampling
• Vacuum-assisted sampling is usually adequate to establish a diagnosis and plan surgical therapy, if needed
• On the other hand, surgical excision of either of these complex cysts would give the pathologist the advantage of examining the entire specimen intact
• References:
  • D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA. ACR BI-RADS^® Atlas: Breast Imaging Reporting and Data System, 5^th ed. Reston, VA: American College of Radiology; 2013.
  • Berg WA, Sechtin AC, Marques H, Zhang Z. Cystic breast masses and the ACRIN 666 experience. Radiol Clin North Am. 2010;48(5):931-987.
  • Stavros AT. Sonographic evaluation of breast cysts. In: Stavros AT. Breast Ultrasound. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:276-350.