Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

Adenoid Cystic Carcinoma of the Breast

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Adenoid cystic carcinoma of the breast:
    • Is a very rare subtype of breast cancer
    • It is usually triple negative
    • It is much less likely to have nodal involvement and is more common in postmenopausal women:
      • With a mean age of 66
    • Distant metastases are rare:
      • However, the lung is the most common site
  • It has a better prognosis than infiltrating ductal triple negative breast cancer:
    • With a 5-year overall survival rate of 88%.3
  • References
    • Treitl D, Radkani P, Rizer M, El Hussein S, Paramo JC, Mesko TW. Adenoid cystic carcinoma of the breast, 20 years of experience in a single center with review of literature. Breast Cancer. 2018;25(1)28-33.
    • Welsh JL, Keeney MG, Hoskin TL, et al. Is axillary surgery beneficial for patients with adenoid cystic carcinoma of the breast? J Surg Oncol. 2017;116(6):690-695.
    • Kulkarni N, Pezzi CM, Greif JM, et al. Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base. Ann Surg Oncol. 2013;20(7):2236-2241

Prohylactic Mastectomy / Risk Reducing Mastectomy

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • In the last 10 years there has been a significant focus on the role of contralateral prophylactic mastectomy and the risk of contralateral breast cancer
  • Single-institution studies and Surveillance, Epidemiology, and End Results program (SEER) data:
    • Have found contralateral prophylactic mastectomy rates to be as high as 25%:
      • Which continue to increase
        • Further, this trend seems to be limited to the United States
  • Nichols et al:
    • Reviewed rates of contralateral breast cancer between 1976 and 2006 using the SEER database
    • Overall, they found the rate of contralateral breast cancer to be declining:
      • Approximately 3% per year since 1985
    • From 1990 forward, they found this benefit to be restricted to those presenting with an ER+ breast cancer:
      • With annual incidence rates of contralateral breast cancer of 0.25% to 0.37%:
        • When the index cancer was diagnosed after age 30 years
    • The rates of contralateral breast cancer were higher in patients with ER– negative breast cancers:
      • But still remained reasonably low with annual incidence rates of contralateral breast cancer of 0.45% to 0.65% when the index cancer was diagnosed after age 40 years
  • The use of adjuvant endocrine therapy:
    • Has contributed to this decline as it reduces the risk of contralateral breast cancer by approximately 50%
  • Contralateral prophylactic mastectomy:
    • Is attributed with approximately a 90% to 94% overall reduction in the risk of contralateral breast cancer:
      • Not 100%
  • Contralateral prophylactic mastectomy:
    • Does not improve overall survival:
      • Recent modeling suggests the added absolute benefit of contralateral prophylactic mastectomy to overall survival:
        • Is less than 1.45%
  • The American Society of Breast Surgeons published a consensus statement with indications and suggestions for patient management and decision making with regard to contralateral prophylactic mastectomy:
    • Discouraging the procedure for women with unilateral breast cancer at average risk for contralateral cancer
  • References
    • Nichols HB, Berrington de Gonzalez A, Lacey JV, Rosenberg PS, Anderson WF. Declining incidence of contralateral breast cancer in the United States from 1975 to 2006. J Clin Oncol. 2011;29(12):1564-1569.
    • Early Breast Cancer Trialists’ Collaborative Group, Davies C, Godwin J, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771-784.
    • King TA, Sakr R, Patil S, et al. Clinical management factors contribute to the decision for contralateral prophylactic mastectomy. J Clin Oncol. 2011;29(16):2158-2164.
    • Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22(12):2328-2335.
    • Portschy PR, Kuntz KM, Tuttle TM. Survival outcomes after contralateral prophylactic mastectomy: a decision analysis. J Natl Cancer Inst. 2014;106(8).
    • Boughey JC, Attai DJ, Chen SL, et. al.. Contralateral prophylactic mastectomy consensus statement from the American Society of Breast Surgeons: additional considerations and a framework for shared decision making. Ann Surg Oncol. 2016 Oct;23(10):3106-3111.

Contralateral Mastectomy (CM) Rates in the USA.

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • In the United States (US), CM rates have been increasing for more than two decades:
    • One study using the Surveillance, Epidemiology, and End Results (SEER) database:
      • Showed that the rates of CM in patients with unilateral breast cancer (UBC) undergoing mastectomy increased:
        • From 4.2% in 1998 to 11.0% in 2003
    • A similar study using the National Cancer Database (NCDB):
      • Showed that the CM rate increased from 0.4% in 1998 to 4.7% in 2007
    • Since then, several other studies have demonstrated a continuation of this trend in the US:
      • Reporting CM rates as high as 30% to 50% in certain patient populations
  • This trend of increasing CM rates has also been seen in patients with ductal carcinoma in situ
  • Factors associated with undergoing CM are:
    • Caucasian race
    • Private insurance
    • Higher socioeconomic status
    • High volume centers
    • Younger age
    • Use of breast MRI
    • Genetic testing
    • Reconstructive surgery
  • Surgeons have also been shown to influence the likelihood of CM:
    • For example, if a surgeon recommends against CM:
      • The likelihood of undergoing CM decreases:
        • In a survey study of patients who underwent definitive surgery for breast cancer:
          • Those whose surgeons recommended against CM had a CM rate of 6.1%:
            • Whereas those who received no recommendation had a CM rate of 57.5
  • Shared decision making has been shown to reduce decision-related conflict and regret

Screening for Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The average lifetime risk of breast cancer for women in the United States:
    • Is 12.9%
  • Age is one of the most important risk factors:
    • The median age of diagnosis is 63 years:
      • With over 50% of breast cancer diagnoses occurring:
        • Between the ages of 55 to 74 years
    • Breast cancer diagnosis drops from 26.5% to 13.7% for women ages 75 years or older and to 5.2% for women aged 84 years or older
  • Mammogram:
    • Remains the cornerstone for screening
  • There is little guidance for continued screening recommendations for women aged 75 years or older:
    • In 2009, the U.S. Preventive Services Task Force:
      • Made official recommendations that women have biennial screening mammography:
        • From aged 50 to 74 years
      • For women aged 40 to 49 years:
        • Screening should be done based on individual assessment and discussion with her health care providers
      • The task force concluded that the data to evaluate the benefit and harms for mammography for women over age 75 years was insufficient to recommend continued screening
    • The American Cancer Society and the American Society of Breast Surgeons:
      • Recommend continued screening:
        • As long as a woman’s life expectancy is at least 10 years:
          • There has been demonstrated survival benefit in this population without significant comorbidities as well as lower rates of false-positive biopsies
  • The Affordable Care Act includes coverage of screening mammography regardless of life expectancy
  • The recommendation to stop screening mammograms based on advanced age or competing comorbidities is difficult for both patients and providers to approach and discuss
  • Some patients think that stopping screening is a form of age discrimination and providers find it difficult to discuss or determine life expectancy
  • Age is an unreliable indicator of mortality:
    • The Lee Index was initially validated as a tool to estimate 4-year mortality
    • This was recently re-evaluated and validated for 10-year mortality
    • The index can be accessed through the ePrognosis website:
    • Patients with a high 10-year mortality risk are more likely to be harmed by preventive interventions with “long lagtimes-to-benefits” such as screening mammograms
  • The diagnosis of occult malignancy in elderly patients:
    • Has the risk of causing harm related to diagnostic procedures, surgical procedures, and medical or radiation therapies
    • It is estimated that approximately 30% of breast cancers are overdiagnosed cancers and almost one third of the women will experience a harm related to this overdiagnosis
  • For older women with a life expectancy of greater than 5 to 10 years:
    • It is unknown whether screening mammography actually decreases the risk of dying of breast cancer
  • For elderly women with new symptomatic breast findings:
    • Diagnostic imaging will guide diagnosis and treatment
  • Mammography is more sensitive and specific for women over 80 years of age (sensitivity = 86% vs. 73% in 50-year-old; specificity = 94% vs. 92% in 50-year-old)
  • Ultrasound is also a reliable imaging test and biopsy can be safely done with relative patient comfort for histologic and biologic/prognostic panel testing
  • This information will then allow for an informed shared decision-making discussion with the patient and her provider
  • References
  • Cancer Stat Facts: Female Breast Cancer. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Accessed March 3, 2023. https://seer.cancer.gov/statfacts/html/breast.html
  • Nelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med. 2016;164(4):244-255. doi.org/10.7326/M15-096
  • The American Society of Breast Surgeons Official Statements. Accessed March 3, 2023. https://www.breastsurgeons.org/resources/statements
  • Cruz M, Covinsky K, Widera EW, Stijacic-Cenzer I, Lee SJ. Accurately predicting 10-year mortality for older Americans: an extension of the Lee Index. JAMA. 2013;309(9):874-876. doi.org/10.1001/jama.2013.1184
  • ePrognosis—Lee Index. University of California San Francisco. Accessed March 3, 2023. https://eprognosis.ucsf.edu/lee.php
  • Walter LC, Schonberg MA. Screening mammography in older women: a review. JAMA. 2014;311(13):1336-1347. doi.org/10.1001/jama.2014.2834

Axillary Lymphadenopathy

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Isolated axillary adenopathy:
    • Is usually benign and resolves spontaneously
  • Persistent adenopathy of a malignant nature:
    • Is most commonly due to:
      • Lymphoma in men
      • In women:
        • Breast cancer predominates:
          • Followed by lymphoma and melanoma
  • Even so, the incidence of occult primary breast cancer with axillary metastases:
    • Comprises only 0.3 to 0.8% of all newly diagnosed breast carcinomas:
      • It is classified by the American Joint Commission on Cancer as:
        • CT0, cN1, cM0, stage 2A
  • When evaluating a woman with malignant adenopathy, the differential diagnosis must also include:
    • Lung
    • Ovary
    • Thyroid
    • Gastrointestinal tract
    • Liver
    • Pancreas
    • Kidney
  • Initial workup after a complete history and physical examination (including skin survey) should include:
    • A bilateral mammogram and an ultrasound:
      • If the mammogram and ultrasound are negative, a breast MRI is appropriate, followed by chest x-ray and CT scans if the MRI is unrevealing
  • References
    • Rueth NM, Black DM, Limmer AR, et al. Breast conservation in the setting of contemporary multimodality treatment provides excellent outcomes for patients with occult primary breast cancer. Ann Surg Oncol. 2015;22(1):90-95.
    • NCCN Guideline with NCCN Evidence Blocks™ – Breast Cancer Version 3.2019. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/recently_updated.aspx. Accessed September 21, 2019

The Role of Surgery in Metastatic Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The role of locoregional treatment in the setting of de novo metastatic breast cancer:
    • Is controversial
  • Typically, surgery:
    • Has been reserved for palliation
  • A 2012 meta-analysis of 15 retrospective studies showed:
    • Resection of the primary tumor:
      • Was associated with increased overall survival:
      • OS; HR 0.69, 95% CI 0.63 to 0.77, P<0.00001
    • Unfortunately, recent prospective studies have shown conflicting results:
      • A Turkish study showed improved survival at a median of 40 months follow-up, especially in more indolent forms of breast cancer
      • In contrast, a U.S. study did not show improvement in survival associated with surgery:
        • Determinants of improved survival were related to response to therapy
      • An Italian study showed improvement in survival in patients with HER2 positive disease after first-line trastuzumab-based therapy
      • In addition, an Indian study by Badwe et al. did not show a survival advantage with resection of the primary cancer:
        • At a median follow-up of 23 months, the overall survival was 41.9% in the locoregional surgical arm vs. 43.0% in the non-locoregional treatment arm
  • Each of these studies has potential bias flaws but:
    • Show potential benefit of resection in select patients with high functional status and good response to optimal systemic therapy
  • While awaiting the results of ECOG E2108 clinical trial:
    • Surgery in stage IV breast cancer patients should be discussed in a multidisciplinary setting:
      • Taking into account comorbidities, response to therapy, and tumor burden.
  • References
    • Poggio F, Lambertini M, de Azambuja E. Controversies in oncology: Surgery of the primary tumour in patients presenting with de novo metastatic breast cancer: to do or not to do? ESMO Open 2018;3:e000324.
    • Wu SG, Zhang WW, Sun JY, et al. The survival benefits of local surgery in stage IV breast cancer are not affected by breast cancer subtypes: a population-based analysis. Oncotarget. 2017;8(40):67851-67860. Published 2017 Jun 29.
    • Soran A, Ozmen V, Ozbas S, et al. randomized trial comparing resection of primary tumor with no surgery in Stage IV breast cancer at presentation: Protocol MF07-01. Ann Surg Oncol. 2018;25(11): 3141-3149.
    • R Badwe, R Hawaldar, N Nair, et al.: Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol. 2015;16(13):1380-1388

Indications for Risk Reducing Mastectomy (RRM)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • According to National Comprehensive Cancer Network (NCCN) guidelines:
    • Risk Reducing Mastectomy (RRM) should be discussed with patients having the following genetic mutations:
      • BRCA 1
      • BRCA 2
      • Li Fraumeni Syndrome
      • PTEN
      • History of Mantle Radiation Prior to the age of 30
  • There is insufficient evidence in CHEK2 mutations to routinely recommend RRM
  • Risk-reducing mastectomy has been shown to decrease the incidence of breast cancer by 90% or more in several studies
  • References
    • Hartmann LC, Lindor NM. The role of risk-reducing surgery in hereditary breast and ovarian cancer. N Engl J Med. 2016;374(5):454-468.
    • NCCN Guideline with NCCN Evidence Blocks™ – Breast Cancer Version 4.2024. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/recently_updated.aspx. Accessed August 16, 2024.
    • Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004;22(6):1055-1062.
    • Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA2010;304(9):967-975

Risk Reducing Salpingo-Oophorectomy (RRSO) in BRCA Carriers

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • BRCA 1 carriers:
    • Are at increased risk of:
      • Breast
      • Ovarian
      • Prostate
      • Pancreatic cancer
      • Melanoma
  • RRSO is recommended between:
    • Ages 35 to 40 in BRCA 1
    • Ages 40 to 45 in BRCA2 carriers, or
      • When done having children
  • RRSO has been shown to reduce the risk of breast cancer:
    • In premenopausal women by about 50%
  • RRSO has also been shown to reduce the risk of ovarian cancer by 80%
  • In women who have not undergone RRSO, surveillance with CA 125 and pelvic ultrasound:
    • May be considered at the clinician’s discretion beginning ages 30 to 35
  • References
    • NCCN Guideline with NCCN Evidence Blocks™ – Breast Cancer Version 4.2024. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/recently_updated.aspx. Accessed August 16, 2024.
    • Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101(2):80-87

Interrupting Endocrine Therapy to Attempt Pregnancyafter Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • N Engl J Med 2023;388:1645-1656
  • Background:
    • Prospective data on the risk of recurrence among women with hormone receptor–positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking
  • Methods:
    • They conducted a single-group trial in which they evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer
    • Eligible women were who desired to get pregnant were:
      • 42 years of age or younger
      • Had had stage I, II, or III disease
      • Had received adjuvant endocrine therapy for 18 to 30 months
    • The primary end point was the number of breast cancer events:
      • Defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer during follow-up
    • The primary analysis was planned to be performed after 1600 patient-years of follow-up
    • The prespecified safety threshold was the occurrence of 46 breast cancer events during this period
    • Breast cancer outcomes in this treatment interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial
  • Results:
    • Among 516 women:
      • The median age was 37 years
      • The median time from breast cancer diagnosis to enrollment was 29 months
      • 93.4% had stage I or II disease
    • Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth
    • In total, 365 babies were born
    • At 1638 patient-years of follow-up (median follow-up, 41 months):
      • 44 patients had a breast cancer event, a result that did not exceed the safety threshold
    • The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort
  • Conclusions:
  • Among select women with previous hormone receptor–positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort
  • Further follow-up is critical to inform long-term safety

Contralateral Mastectomy (CM) for Breast Cancer Indications

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Recommendations for the use of contralateral mastectomy in patients with unilateral breast cancer