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.

Breast Cancer Chemoprevention Medications

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Postmenopausal women with a uterus:
    • Are at a higher risk of developing uterine cancer with tamoxifen:
      • Therefore raloxifene is preferred in this subset
  • Tamoxifen:
    • Provides a slightly higher breast cancer risk reduction compared to raloxifene
  • Raloxifene:
    • Has a slightly lower rate of developing venous thromboembolism (VTE) than tamoxifen
    • It is preferred in patients with osteoporosis
  • Tamoxifen:
    • Is the chemoprevention agent of choice in premenopausal women and in postmenopausal women who have undergone a hysterectomy
  • Aromatase inhibitors:
    • Are another option for chemoprevention and are used:
      • In patients with contraindications to selective estrogen receptor modulator SERM use (history of VTE, stroke risk):
        • But have a significant incidence of musculoskeletal pain and worsening of osteoporosis
  • Fulvestrant, nor leuprolide are used for chemoprevention
  • References:
    • Reimers LL, Sivasubramanian PS, Hershman D, et al. Breast cancer chemoprevention among high-risk women and those with ductal carcinoma in situ. Breast J. 2015;21(4):377-386.
    • Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast, Fifth Edition. Philadelphia, PA: Wolters Kluwer Health, 2014.
    • Thorat MA, Cuzick J. Preventing invasive breast cancer using endocrine therapy. Breast. 2017;34(Suppl 1):S47-s54.

PTEN Mutation and Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Phosphatase and Tensin Homolog (PTEN):
    • Is a tumor suppressor gene, and inherited mutations in this gene can be associated with Cowden’s syndrome
  • Cowden’s syndrome:
    • Is associated with increased risk of multiple types of cancer including:
      • Breast
      • Endometrial
      • Thyroid
      • Colorectal
      • Melanoma
  • PTEN mutations carriers:
    • Tend to develop cancers at younger ages than individuals with sporadic malignancies
    • Lifetime breast cancer risk with this syndrome is up to 85%:
      • As reported by Tan el al., although it is noted given the limitations in reported studies of women with Cowden’s syndrome, risk estimates are not stable
    • Hamartomas on the skin or mucous membranes are extremely common in this syndrome
    • Macrocephaly may also be seen
  • PTEN mutations are inherited in an autosomal dominant pattern with an estimated frequency of 1 in 200,000 people
  • Loss of PTEN gene expression at the somatic or germline level:
    • May affect response to HER2-directed therapies, and low levels of the protein in stromal cells have been associated with increased risk of recurrence related to radiation in pre-clinical models
  • The other genes with moderate risk of developing breast cancer with the following relative risks reported from a meta-analysis:
    • PALB2 RR 5.3
    • CDH1 RR 6.6
    • CHEK2 truncating mutations RR 3.0
    • ATM RR 2.8
  • References
    • Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol.2017;3(9):1190-1196.
    • Gustafson S, Zbuk KM, Scacheri C, Eng C. Cowden syndrome. Semin Oncol.2007;34(5):428-434.
    • Ngeow J, Sesock K, Eng C. Breast cancer risk and clinical implications for germline PTEN mutation carriers. Breast Cancer Res Treat. 2017;165(1):1-8.
    • Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18(2):400-407.
    • Weiss A, Garber JE, King T. Breast cancer surgical risk reduction for patients with inherited mutations in moderate penetrance genes. JAMA Surg. 2018;153(12):1145-1146.
    • Kim C, Lee CK, Chon HJ, et al. PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer. Oncotarget. 2017;8(69):113494-113501.
    • Sizemore GM, Balakrishnan S, Thies KA, et al. Stromal PTEN determines mammary epithelial response to radiotherapy. Nat Commun. 2018;9(1):2783.
    • Easton DF, Pharoah PD, Antoniou AC, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med. 2015;372(23):2243-2257.
Cancer Surgeon
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Chemoprevention for Women at High Risk Breast Canacer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Tamoxifen and raloxifene:
    • Reduce the risk of invasive breast cancer in high-risk women when compared to placebo:
      • But are associated with increased vasomotor symptoms
    • In the NSABP P-2 / STAR trial:
      • When compared to raloxifene:
        • Tamoxifen use resulted in higher rates of uterine cancer (2/1000 vs. 1.5/1000), deep vein thrombosis (2.29/1000 vs 1.69/1000), and pulmonary embolism (1.41/1000 vs. 0.96/1000)
  • Aromatase inhibitors:
    • Are not associated with a risk of thrombosis
  • Use of concomitant hormone replacement therapy with tamoxifen or raloxifene:
    • Was not allowed in the STAR trial and is discouraged in the 2013 American Society of Clinical Oncology chemoprevention guidelines
  • In the MAP.3 prevention trial:
    • Exemestane significantly reduced the incidence of invasive breast cancer
    • Was not associated with serious adverse effects, and resulted in only minimal changes in health-related quality of life:
      • However, it is not FDA-approved for chemoprevention of breast cancer but can be used in an off-label manner
    • Decision tables weighing the risks and benefits of chemoprevention agents:
      • Are available and can identify the most appropriate drug with the fewest side effects for each individual patient
  • Compliance with chemoprevention varies by the agent used:
    • In the MAP.3 trial:
      • 85% of enrolled women were compliant with exemestane
    • In the NSABP P-1 trial:
      • 76% of women with compliant with tamoxifen
    • In clinical practice, overall compliance with chemoprevention is even lower:
      • With a study by Flanagan and colleagues reporting a 61% rate of completion of planned chemoprevention in high-risk patients
  • References
    • Visvanathan K, Hurley P, Bantug E, Brown P, Col NF, Cuzick J, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31(23):2942-2962.
    • Freedman AN, Yu B, Gail MH, Costantino JP, Graubard BI, Vogel VG, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29(17):2327-2333.
    • Goss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381-2391.
    • Nelson HD, Fu R, Humphrey L, et al. Comparative Effectiveness of Medications To Reduce Risk of Primary Breast Cancer in Women [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Sep. (AHRQ Comparative Effectiveness Reviews, No. 17.)
    • Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371-1388.
    • Flanagan MR, Zabor EC, Stempel M, Mangino DA, Morrow M, Pilewskie ML. Chemoprevention Uptake for Breast Cancer Risk Reduction Varies by Risk Factor. Ann Surg Oncol. 2019;26(7):2127-2135.
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What Does it Mean to Have a CHEK2 Mutation?

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Truncating CHEK2 mutations (such as the c.1100delC mutation):
    • Are considered rare, moderate penetrance mutations
  • The lifetime risk of developing breast cancer with these mutations:
    • Is 3 times higher than the general population:
      • This means that the majority of patients with these mutations will not develop breast cancer, and many of the cancers that do develop may be sporadic and not related to the mutation:
        • Patients with these mutations should be counseled about their risk and the available risk management strategies
  • Those with a significant family history of breast cancer:
    • Should be counseled regarding high risk breast cancer screening:
      • Annual mammogram with consideration of annual MRI starting at age 40 or modified to an earlier age based on family history
    • Should be counseled regarding prevention strategies, including:
      • Chemoprevention and prophylactic surgery
  • It should be emphasized that there is less absolute risk-reduction benefit with prophylactic surgery compared to high-penetrance mutations like BRCA mutations, and recommendations should be based on patient’s family history
  • National Comprehensive Cancer Network guidelines:
    • Should be followed with recommendation for high-risk screening, including colon cancer screening recommendations among individuals with a CHEK2 mutation
  • References
    • Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat Genet. 2008;40(1):17-22.
    • Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, et al. Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol. 2015;1(7):943-951.
    • Weiss A, Garber JE, King T. Breast cancer surgical risk reduction for patients with inherited mutations in moderate penetrance genes. JAMA Surg. 2018;153(12):1145-1146.
    • Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13(9):581-588.
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What Does it Mean to Have a CHEK2 Mutation?

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Truncating CHEK2 mutations (such as the c.1100delC mutation):
    • Are considered rare, moderate penetrance mutations
  • The lifetime risk of developing breast cancer with these mutations:
    • Is 3 times higher than the general population:
      • This means that the majority of patients with these mutations will not develop breast cancer, and many of the cancers that do develop may be sporadic and not related to the mutation:
        • Patients with these mutations should be counseled about their risk and the available risk management strategies
  • Those with a significant family history of breast cancer:
    • Should be counseled regarding high risk breast cancer screening:
      • Annual mammogram with consideration of annual MRI starting at age 40 or modified to an earlier age based on family history
    • Should be counseled regarding prevention strategies, including:
      • Chemoprevention and prophylactic surgery
  • It should be emphasized that there is less absolute risk-reduction benefit with prophylactic surgery compared to high-penetrance mutations like BRCA mutations, and recommendations should be based on patient’s family history
  • National Comprehensive Cancer Network guidelines:
    • Should be followed with recommendation for high-risk screening, including colon cancer screening recommendations among individuals with a CHEK2 mutation
  • References
    • Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat Genet. 2008;40(1):17-22.
    • Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, et al. Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol. 2015;1(7):943-951.
    • Weiss A, Garber JE, King T. Breast cancer surgical risk reduction for patients with inherited mutations in moderate penetrance genes. JAMA Surg. 2018;153(12):1145-1146.
    • Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13(9):581-588.
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CDH 1 Mutation and Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Recognizing family history patterns associated with specific gene mutations is important
  • A family history of invasive lobular cancer and gastric cancer may be associated with CDH1 mutations:
    • These mutations confer a 6.6 times greater risk of breast cancer than the general population and are associated with a high risk of hereditary diffuse gastric cancer (55% to 80%)
  • Patients with CDH1 mutations:
    • Should be offered prophylactic gastrectomy and consideration of bilateral prophylactic mastectomy based on family history
    • If surgery is not pursued, guidelines for screening for gastric cancer include:
      • Yearly endoscopic surveillance with random mucosal biopsies
    • Breast screening consists of:
      • Annual mammogram and breast MRI
  • References
    • Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol.2015;1(1):23-32.
    • Weiss A, Garber JE, King T. Breast cancer surgical risk reduction for patients with inherited mutations in moderate penetrance genes. JAMA Surg. 2018;153(12):1145-1146
    • van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, et al . Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015;52(6):361-374.
    • National Comprehensive Cancer Network Guidelines. Genetic/familial high-risk assessment: breast and ovarian, Version 1/2018. https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed November 9, 2019.
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Risk Assessments Models in Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The Gail model:
    • Which is based on age, race/ethnicity, age at menarche, age at first live birth, number of prior breast biopsies, personal history of atypical hyperplasia, and family history of breast cancer in first-degree relatives:
      • Does not address and is not appropriate for patients with lobular carcinoma in situ (LCIS)
  • The Tyrer-Cuzick model:
    • Incorporates age, nulliparity, family history, and LCIS
    • In addition, the Tyrer-Cuzick model incorporates:
      • BMI, age at menarche, age at menopause, hormone replacement therapy use, and prior breast biopsies
    • However, while the Tyrer-Cuzick model does incorporate personal history of atypical ductal hyperplasia and LCIS:
      • Data has emerged showing that this model appears to overestimate risk and has poor concordance among populations of women with high-risk breast lesions
    • This model does not accurately predict invasive breast cancer risk and should be avoided even if it may be the most accurate in assessing risk secondary to family history, among women with LCIS
    • Breast cancer risk among women with LCIS has been shown to be approximately 2% per year and modified by volume of LCIS
  • BRCAPRO and BOADICEA:
    • Are both Mendelian models that estimate breast cancer risk based on the probability that the individual carries a mutation in a major breast cancer susceptibility gene, such as BRCA1 or BRCA2
    • The BOADICEA model incorporates 3rd-degree relatives, whereas the BRCAPRO only incorporates 1st- and 2nd-degree relatives
    • Neither of these models incorporate nulliparity or LCIS into the calculation
  • References:
    • Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989;81(24):1879-1886.
    • Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med. 2004;23(7):1111-1130. [See comment in Stat Med. 2005;24:1610-1612; erratum appears in Stat Med. 2005;24:156].
    • Valero M, Zabor E, Park A, Gilbert E, Newman A, King TA, et al. The Tyrer-Cuzick Model inaccurately predicts invasive breast cancer risk in women with LCIS. Ann Surg Oncol. 2020;27(3):736-740.
    • Boughey JC, Hartmann LC, Anderson SS, Degnim AC, Vierkant RA, Reynolds CA, et al. Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) model for breast cancer risk prediction in women with atypical hyperplasia. J Clin Oncol. 2010;28(22):3591-3596.
    • King TA, Pilewskie M, Muhsen S, Patil S, Mautner SK, Park A, et al. Lobular carcinoma in situ: a 29-year longitudinal experience evaluating clinicopathologic features and breast cancer risk. J Clin Oncol. 2015;33(33):3945-3952.
    • Berry DA, Parmigiani G, Sanchez J, Schildkraut J, Winer E. Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history. J Natl Cancer Inst. 1997;89(3):227-238.
    • Antoniou AC, Pharoah PP, Smith P, Easton DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer. 2004;91(8):1580-1590.
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Tucatinib Plus T-DM1 May Benefit Patients With Advanced or Metastatic HER2-Positive Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • A combination of two HER2-targeted drugs – tucatinib and ado-trastuzumab emtansine (T-DM1), extended progression-free survival among patients with unresectable, locally advanced, or metastatic HER2-positive breast cancer compared with T-DM1 alone, according to results from the HER2CLIMB-02 trial presented at the 2023 San Antonio Breast Cancer Symposium (Abstract GS01-10).
  • Study Background
    • T-DM1 is an antibody-drug conjugate consisting of trastuzumab and the cytotoxic drug emtansine. It was approved by the U.S. Food and Drug Administration for use as a monotherapy in 2013 for patients with late-stage HER2-positive breast cancer, and in 2019 for patients with early-stage HER2-positive breast cancer. However, not all patients have durable responses to T-DM1, and a combination approach may boost the drug’s efficacy.
  • Tucatinib, a small-molecule inhibitor of HER2, has been shown to delay disease progression in the central nervous system, unlike most other HER2-targeted drugs. For patients with brain metastases, such a drug can make a significant difference.
    • HER2-positive breast cancer has a predilection to spread to the brain, and when this occurs, prognosis is poor.
    • Few options exist for the successful management of breast cancer brain metastases, making this an area of unmet need.
  • HER2CLIMB and HER2CLIMB-02:
    • A previous trial, HER2CLIMB, found that the addition of tucatinib to a regimen containing the HER2-targeted antibody trastuzumab and the chemotherapy capecitabine significantly improved progression-free and overall survival in heavily pretreated patients, including those with brain metastases. This trial led to the 2020 approval of tucatinib, trastuzumab, and capecitabine by the U.S. Food and Drug Administration.
  • In the phase III HER2CLIMB-02 trial, 463 patients with unresectable, locally advanced, or metastatic HER2-positive breast cancer were enrolled and randomly assigned to receive tucatinib plus T-DM1 (n = 228) or placebo plus T-DM1 (n = 235). Among these patients, 44.1% had brain metastases at baseline.
    • The median time to disease progression or death was 9.5 months for patients in the tucatinib arm and 7.4 months for patients in the placebo arm, with tucatinib plus T-DM1 reducing the risk of disease progression or death by 24.1%.
    • Among patients who had brain metastases at baseline, the median time to disease progression or death was 7.8 months for those in the tucatinib arm and 5.7 months for those treated in the placebo arm, with tucatinib plus T-DM1 reducing the risk of disease progression or death by 36.1%.
    • The overall survival data remain immature after a median of 24.4 months of follow-up.
    • The rate of certain treatment-related side effects, especially those related to liver and gastrointestinal function, was higher among patients treated with tucatinib than those treated with placebo, resulting in a higher rate of dose adjustments and treatment discontinuation in the tucatinib arm.
      • However, these effects were largely manageable with monitoring and clinical intervention.
    • This study is one of very few large breast cancer studies prospectively designed to evaluate novel systemic therapies in patients with brain metastases.
    • While there is much interest in improving outcomes for patients with HER2-positive breast cancer brain metastases, most studies evaluating systemic agents have been limited by a small size, a retrospective design, or an exploratory analysis of a larger study.
  • Limitations of this study include as-yet immature overall survival data.
    • Further, the study was not designed to compare tucatinib plus T-DM1 to tucatinib plus trastuzumab and capecitabine or any regimens containing the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd).

Variant of Unknown Significance (VUS) In Hereditary Breast Cancer Tests

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • When patients are told they have a variant of unknown significance (VUS):
    • It can often lead to anxiety and overtreatment
  • It is important to counsel patients that a VUS:
    • Is not clinically actionable and the majority of VUS are reclassified as benign
  • Patients should be counseled to update their genetic counselors as their family history changes and keep contact information up to date as variant reclassification does occur
  • The American College of Medical Genetics has recommended that genetic testing classify genetic variants using the following classification schema:
    • Deleterious (pathogenic)
    • Suspected deleterious (likely pathogenic)
    • Variant of Uncertain Clinical Significance
    • Genetic variant, favor polymorphism (likely benign)
    • Polymorphism (benign)
  • While deleterious and suspected deleterious mutations of BRCA mutations:
    • Are known to be associated with an increased risk of breast and ovarian cancer:
      • It is unknown whether a BRCA VUS mutation is associated with an increased risk due to limited available data
      • As the use of genetic testing increases and as more of the population is tested, the knowledge base regarding variant pathogenicity constantly grows
  • Given the amount of data available from many years of BRCA1 / BRCA 2 testing:
    • The prevalence of VUS among this population has declined to 2% to 5%:
      • However, among moderate and low penetrance genes:
        • The number of VUS continues to rise
      • As the data expand and knowledge regarding a variant evolves, a variant may be reclassified
  • In a study reported in the Journal of the American Medical Association:
    • 25.4% of patients initially diagnosed with a VUS were reclassified over a 12-year period
    • Of these patients, 97% were downgraded to benign or likely benign
    • Three percent of patients were upgraded to pathogenic or likely pathogenic variants
  • Given this low risk of reclassification to pathogenic mutation, risk-reducing mastectomy, salpingo-oophorectomy, or genetic testing of family members are not indicated for this patient
  • There is currently no established effective screening protocol for pancreatic cancer, even among patients with a deleterious BRCA 2 mutation
  • References:
    • Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424.
    • Hall MJ, Reid JE, Burbidge LA, Pruss D, Deffenbaugh AM, Frye C, et al. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer. 2009;115(10):2222-2233.
    • Mersch J, Brown N, Pirzadeh-Miller S, Mundt E, Cox HC, Brown K, et al. Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA. 2018;320(12):1266-1274.
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Screening for Breast Cancer in a Patient with a History of Mantle Radiation

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Receipt of mantle field radiation before the age of 30:
    • Is associated with a significantly increased risk of breast cancer compared to the general population
  • Patients with a history of Hodgkin’s lymphoma treated with mantle field radiation therapy:
    • Are more likely to be diagnosed with breast cancer at a younger age, have hormone receptor negative breast cancer, and have a second breast cancer
    • Because the increased risk of breast cancer has been seen as early as 8 years following receipt of radiation therapy:
      • High risk screening after mantle field radiation therapy should begin at the age of 25 or 8 years after radiation therapy, whichever occurs later
    • The estimated cumulative incidence of breast cancer by the age of 50 among patients with a history of Hodgkin’s lymphoma treated with mantle field radiation therapy:
      • Is 35%
  • Among all women at high risk for breast cancer:
    • Lifetime risk greater than 20%:
      • Annual screening MRI:
        • Has been associated with 77% to 100% sensitivity for detecting a new cancer
      • While mammography is associated with 16% to 40% sensitivity
  • In 2007, the American Cancer Society convened an expert panel to review the evidence on MRI screening as an adjunct to annual mammography for women at high risk of developing breast cancer:
    • Annual screening MRI is recommended for patients with:
      • A clinical history of chest radiation between the ages of 10 and 30 years
      • Women with a known BRCA mutation
      • Untested first-degree relatives of BRCA mutation carriers
      • Those with other genetic mutations increasing breast cancer risk
      • Women with a greater than 20% lifetime risk secondary to family history
  • The addition of bilateral breast ultrasound to a screening regimen of mammography and MRI:
    • Is associated with a substantial increase in false positives leading to additional biopsies with no incremental benefit over mammography and MRI alone
  • There is insufficient evidence to recommend for or against annual screening breast MRI in women who have a history of:
    • Lobular carcinoma in situ
    • Atypical lobular hyperplasia
    • Atypical ductal hyperplasia
  • There is no evidence to support MRI in women with:
    • Less than 15% lifetime risk of breast cancer
    • Dense breast tissue
    • Personal history of breast cancer
  • References:
    • Veit-Rubin N, Rapiti E, Massimo U, Benhamou S, Vinh-Hung V, Vlastos G, et al. Risk, characteristics, and prognosis of breast cancer after Hodgkin’s lymphoma.Oncologist. 2012;17(6):783-791.
    • Henderson TO, Amsterdam A, Bhatia S, Hudson MM, Meadows AT, Neglia JP, et al. Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med. 2010;152(7):444-455; w144-454.
    • Moskowitz CS, Chou JF, Wolden SL, Bernstein JL, Malhotra J, Novetsky Friedman D, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol.2014; 32(21):2217-2223.
    • Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57(2):75-89.
    • National Comprehensive Cancer Network. Breast Cancer Screening and Diagnosis, Version 1.2019. https://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf. Accessed February 23, 2020.
    • Riedl CC, Luft N, Bernhart C, Weber M, Bernathova M, Tea MK, et al. Triple-modality screening trial for familial breast cancer underlines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density. J Clin Oncol. 2015;33(10):1128-1135.
    • van Zelst JCM, Mus RDM, Woldringh G, et al. Surveillance of Women with the BRCA1 or BRCA2 Mutation by Using Biannual Automated Breast US, MR Imaging, and Mammography. Radiology. 2017;285(2):376-388.
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