How to better identify and manage women with elevated breast cancer risk

<?xml version="1.0" encoding="UTF-8"?>
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>Schrager0622</fileName> <TBEID>0C0298E4.SIG</TBEID> <TBUniqueIdentifier>NJ_0C0298E4</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname>How to better identify and&#13;mana</storyname> <articleType>1</articleType> <TBLocation>Copyfitting-JFP</TBLocation> <QCDate/> <firstPublished>20220613T094102</firstPublished> <LastPublished>20220613T094102</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20220613T094102</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Sarina Schrager, MD, MS;&#13;Brenna Bomcamp, BS</byline> <bylineText/> <bylineFull>Sarina Schrager, MD, MS;&#13;Brenna Bomcamp, BS</bylineFull> <bylineTitleText>Sarina Schrager, MD, MS, Professor, Department of Family Medicine and Community Health, University of Wisconsin, 1100 Delaplaine Court, Madison, WI 53715; sbschrag@wisc.edu Sarina Schrager, MD, MS; Brenna Bomcamp, BS; Elizabeth Burnside, MD, MPH, MS Department of Family Medicine (Dr. Schrager) and Department of Radiology (Dr. Burnside), University of Wisconsin, Madison; University of Wisconsin School of Medicine and Public Health, Madison (Ms. Bomcamp) </bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange>199-205</pageRange> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>Breast cancer is the most common invasive cancer in women in the United States; it is estimated that there will be 287,850 new cases of breast cancer in the Uni</metaDescription> <articlePDF>286933</articlePDF> <teaserImage/> <title>How to better identify and manage women with elevated breast cancer risk</title> <deck>This case-based review details screening and management strategies that can maximize the care you provide to women at heightened risk.</deck> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2022</pubPubdateYear> <pubPubdateMonth>June</pubPubdateMonth> <pubPubdateDay/> <pubVolume>71</pubVolume> <pubNumber>5</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>3167</CMSID> </CMSIDs> <keywords> <keyword>genetics</keyword> <keyword> oncology</keyword> <keyword> women's health</keyword> <keyword> breast cancer</keyword> </keywords> <seeAlsos/> <publications_g> <publicationData> <publicationCode>jfp</publicationCode> <pubIssueName>June 2022</pubIssueName> <pubArticleType>Applied Evidence | 3167</pubArticleType> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">30</term> </publications> <sections> <term canonical="true">40</term> </sections> <topics> <term>263</term> <term>28084</term> <term canonical="true">322</term> </topics> <links> <link> <itemClass qcode="ninat:composite"/> <altRep contenttype="application/pdf">images/1800213d.PDF</altRep> <description role="drol:caption"/> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>How to better identify and manage women with elevated breast cancer risk</title> <deck>This case-based review details screening and management strategies that can maximize the care you provide to women at heightened risk.</deck> </itemMeta> <itemContent> <p><span class="dropcap">B</span>reast cancer is the most common invasive cancer in women in the United States; it is estimated that there will be 287,850 new cases of breast cancer in the United States during 2022 with 43,250 deaths.¹ Lives are extended and saved every day because of a robust arsenal of treatments and interventions available to those who have been given a diagnosis of breast cancer. And, of course, lives are also extended and saved when we identify women at risk and provide early interventions. But in busy offices where time is short and there are competing demands on our time, proper assessment of a woman’s risk of breast cancer does not always happen. As a result, women with a higher risk of breast cancer may not be getting appropriate management.^2,3 </p> <p>Familiarizing yourself with several risk-assessment tools and knowing when genetic testing is needed can make a big difference. Knowing the timing of mammograms and magnetic resonance imaging (MRI) for women deemed to be at high risk is also key. The following review employs a case-based approach (with an accompanying <strong>ALGORITHM</strong>) to illustrate how best to identify women who are at heightened risk of breast cancer and maximize their care. We also discuss the chemoprophylaxis regimens that may be used for those at increased risk. </p> <p> <span class="intro"> <caps>Case </caps> </span> u </p> <p>Rachel P, age 37, presents to establish care. She has an Ashkenazi Jewish background and wonders if she should start doing breast cancer screening before age 40. She has 2 children, ages 4 years and 2 years. Her maternal aunt had unilateral breast cancer at age 54, and her maternal grandmother died of ovarian cancer at age 65. </p> <h3>Risk assessment</h3> <p>The risk assessment process (see<strong> ALGORITHM</strong>) must start with either the clinician or the patient initiating the discussion about breast cancer risk. The clinician may initiate the discussion with a new patient or at an annual physical examination. The patient may start the discussion because they are experiencing new breast symptoms, have anxiety about developing breast cancer, or have a family member with a new cancer diagnosis. </p> <p><span class="dingbat3">z</span><span class="intro"> Risk factors. </span>There are single factors that convey enough risk to automatically designate the patient as high risk (see <strong>TABLE 1</strong>^4-9). These factors include having a history of chest radiation between the ages of 10 and 30, a history of breast biopsy with either lobular carcinoma in situ (LCIS) or atypical ductal hyperplasia (ADH), past breast and/or ovarian cancer, and either a family or personal history of a high penetrant genetic variant for breast cancer.^4-9 <br/><br/>In women with previous chest radiation, breast cancer risk correlates with the total dose of radiation.⁵ For women with a personal history of breast cancer, the younger the age at diagnosis, the higher the risk of contralateral breast cancer.⁵ Precancerous changes such as ADH, LCIS, and ductal carcinoma in situ (DCIS) also confer moderate increases in risk. Women with these diagnoses will commonly have follow-up with specialists. <br/><br/><span class="dingbat3">z</span><span class="intro"> </span><span class="intro">Risk assessment tools. </span>There are several models available to assess a woman’s breast cancer risk (see<b> </b><strong>TABLE 2</strong>^10-12<b>)</b>. The Gail model (<a href="https://bcrisktool.cancer.gov/">https://bcrisktool.cancer.gov/</a>) is the oldest, quickest, and most widely known. However, the Gail model only accounts for first-degree relatives diagnosed with breast cancer, may underpredict risk in women with a more extensive family history, and has not been studied in women younger than 35. The International Breast Cancer Intervention Study (IBIS) Risk Evaluation Tool (<a href="https://ibis-risk-calculator.magview.com/">https://ibis-risk-calculator.magview.com/</a>), commonly referred to as the <i>Tyrer-Cuzick model</i>, incorporates second-degree relatives into the prediction model—although women may not know their full family history. The Breast Cancer Surveillance Consortium (BCSC) model (<a href="https://tools.bcsc-scc.org/BC5yearRisk/intro.htm">https://tools.bcsc-scc.org/BC5yearRisk/intro.htm</a>) is the only model that includes breast density in the prediction algorithm. The choice of tool depends on clinician comfort and individual patient risk factors. There is no evidence that one model is better than another.^10-12</p> <p> <span class="intro"> <caps>Case </caps> </span> u </p> <p>Ms. P’s clinician starts with an assessment using the Gail model. However, when the result comes back with average risk, the clinician decides to follow up with the Tyrer-Cuzick model in order to incorporate Ms. P’s multiple ­second-degree relatives with breast and ovarian cancer. (The BCSC model is not an option for Ms. P because she’s never had a mammogram and thus does not have a breast density measurement to include in the model.)</p> <p class="sub1">Genetic testing</p> <p>The National Comprehensive Cancer Network (NCCN) guidelines recommend genetic testing if a woman has a first- or ­second-degree relative with pancreatic cancer, metastatic prostate cancer, male breast cancer, breast cancer at age 45 or younger, 2 or more breast cancers in a single person, 2 or more people on the same side of the family with at least 1 diagnosed at age 50 or younger, or any relative with ovarian cancer (see <strong>TABLE 3</strong>).⁷ Before ordering genetic testing, it is useful to refer the patient to a genetic counselor for a thorough discussion of options. </p> <p>Results of genetic testing may include high-risk variants, moderate-risk variants, and variants of unknown significance (VUS), or be negative for any variants. High-risk variants for breast cancer include <i>BRCA1</i>, <i>BRCA2</i>, <i>PALB2</i>, and cancer syndrome variants such as <i>TP53</i>, <i>PTEN</i>, <i>STK11</i>, and <i>CDH1</i>.^5,6,9,13-15 These high-risk variants confer sufficient risk that women with these mutations are automatically categorized in the high-risk group. It is estimated that high-risk variants account for only 25% of the genetic risk for breast cancer.¹⁶ <br/><br/><i>BRCA1/2</i> and <i>PTEN</i> mutations confer greater than 80% lifetime risk, while other high-risk variants such as <i>TP53</i>, <i>CDH1</i>, and <i>STK11</i> confer risks between 25% and 40%. These variants are also associated with cancers of other organs, depending on the mutation.¹⁷Moderate-risk variants—<i>ATM</i> and <i>CHEK2—</i>do not confer sufficient risk to elevate women into the high-risk group. However, they do qualify these intermediate-risk women to participate in a specialized management strategy.^5,9,13,18 <br/><br/>VUS are those for which the associated risk is unclear, but more research may be done to categorize the risk.⁹ The clinical management of women with VUS usually entails close monitoring. <br/><br/>In an effort to better characterize breast cancer risk using a combination of pathogenic variants found in broad multi-gene cancer predisposition panels, researchers have developed a method to combine risks in a “polygenic risk score” (PRS) that can be used to counsel women (see “What is a polygenic risk score for breast cancer?” on page 203).^19-21PRS predicts an additional 18% of genetic risk in women of European descent.²¹ </p> <p> <span class="intro"> <caps>Case </caps> </span> u </p> <p>Using the assessment results, the clinician talks to Ms. P about her lifetime risk for breast cancer. The Gail model indicates her lifetime risk is 13.3%, just slightly higher than the average (12.5%), and her 5-year risk is 0.5% (average, 0.4%). The IBIS or Tyrer-­Cuzick model, which takes into account her second-degree relatives with breast and ovarian cancer and her Ashkenazi ethnicity (which confers increased risk due to elevated risk of <i>BRCA</i> mutations), predicts her lifetime risk of breast cancer to be 20.4%. This categorizes Ms. P as high risk. </p> <p class="sub1">Enhanced screening recommendations for women at high risk</p> <p><strong>TABLE 4</strong>^8,13,22 summarizes screening recommendations for women deemed to be at high risk for breast cancer. The American Cancer Society (ACS), NCCN, and the American College of Radiology (ACR) recommend that women with at least a 20%<b> </b>lifetime risk have yearly magnetic resonance imaging (MRI) and mammography (staggered so that the patient has 1 test every 6 months) starting 10 years before the age of onset for the youngest affected relative but not before age 30.⁸ For carriers of high-risk (as well as intermediate-risk) genes, NCCN recommends annual MRI screening starting at age 40.¹³ <i>BRCA1/2</i> screening includes annual MRI starting at age 25 and annual mammography every 6 months starting at age 30.²² Clinicians should counsel women with moderate risk factors (elevated breast density; personal history of ADH, LCIS, or DCIS) about the potential risks and benefits of enhanced screening and chemoprophylaxis. </p> <h3>Risk-reduction strategies</h3> <p class="sub1">Chemoprophylaxis</p> <p>The US Preventive Services Task Force (USPSTF) recommends that all women at increased risk for breast cancer consider chemoprophylaxis (<b>B</b> recommendation)²³ based on convincing evidence that 5 years of treatment with either a synthetic estrogen reuptake modulator (SERM) or an aromatase inhibitor (AI) decreases the incidence of estrogen receptor positive breast cancers. (See <strong>TABLE 5</strong><strong>^7,23,24</strong> for absolute risk reduction.) There is no benefit for chemoprophylaxis in women at average risk (<b>D</b> recommendation).²³ It is unclear whether chemoprophylaxis is indicated in women with moderate increased risk (ie, who do not meet the 20% lifetime risk criteria). Chemoprophylaxis may not be effective in women with <i>BRCA1</i> mutations, as they often develop triple-negative breast cancers.<b> </b></p> <p>Accurate risk assessment and shared decision-making enable the clinician and patient to discuss the potential risks and benefits of chemoprophylaxis.^7,24 The USPSTF did not find that any 1 risk prediction tool was better than another to identify women who should be counseled about chemoprophylaxis. Clinicians should counsel all women taking AIs about optimizing bone health with adequate calcium and vitamin D intake and routine bone density tests. </p> <p class="sub1">Surgical risk reduction</p> <p>The NCCN guidelines state that risk-reducing bilateral mastectomy is reserved for individuals with high-risk gene variants and individuals with prior chest radiation between ages 10 and 30.²⁵ NCCN also recommends discussing risk-reducing mastectomy with all women with <i>BRCA</i> mutations.²² </p> <p>Bilateral mastectomy is the most effective method to reduce breast cancer risk and should be discussed after age 25 in women with <i>BRCA</i> mutations and at least 8 years after chest radiation is completed.²⁶ There is a reduction in breast cancer incidence of 90%.²⁵ Breast imaging for screening (mammography or MRI) is not indicated after risk-reducing mastectomy. However, clinical breast examinations of the surgical site are important, because there is a small risk of developing breast cancer in that area.²⁶ <br/><br/>Risk-reducing oophorectomy is the standard of care for women with <i>BRCA</i> mutations to reduce the risk of ovarian cancer. It can also reduce the risk of breast cancer in women with <i>BRCA</i> mutations.²⁷</p> <p> <span class="intro"> <caps>Case </caps> </span> u </p> <p>Based on her risk assessment results, family history, and genetic heritage, Ms. P qualifies for referral to a genetic counselor for discussion of <i>BRCA </i>testing. The clinician discusses adding annual MRI to Ms. P’s breast cancer screening regimen, based on ACS, NCCN, and ACR recommendations, due to her 20.4% lifetime risk. Discussion of whether and when to start chemoprophylaxis is typically based on breast cancer risk, projected benefit, and the potential impact of medication adverse effects. A high-risk woman is eligible for 5 years of chemoprophylaxis (tamoxifen if premenopausal) based on her lifetime risk. The clinician discusses timing with Ms. P, and even though she is finished with childbearing, she would like to wait until she is age 45, which is before the age at which her aunt was given a diagnosis of breast cancer.</p> <h3>Conclusion</h3> <p>Primary care clinicians are well positioned to identify women with an elevated risk of breast cancer and refer them for enhanced screening and chemoprophylaxis (see <strong>ALGORITHM</strong><b>)</b>. Shared decision-making with the inclusion of patient decision aids (<a href="https://decisionaid.ohri.ca/AZsearch.php?criteria=breast+cancer">https://decisionaid.ohri.ca/AZsearch.php?criteria=breast+cancer</a>) about genetic testing, chemoprophylaxis, and prophylactic mastectomy or oophorectomy may help women at intermediate or high risk of breast cancer feel empowered to make decisions about their breast—and overall—health. <span class="end">JFP</span></p> <p class="sub4">Correspondence</p> <p class="reference"> 1. National Cancer Institute. Cancer stat facts: female breast cancer. Accessed May 13, 2022. https://seer.cancer.gov/statfacts/html/breast.html<br/><br/> 2. Guerra CE, Sherman M, Armstrong K. Diffusion of breast cancer risk assessment in primary care. <i>J Am Board Fam Med</i>. 2009;22:272-279. doi:10.3122/jabfm.2009.03.080153<br/><br/> 3. Hamilton JG, Abdiwahab E, Edwards HM, et al. Primary care providers’ cancer genetic testing-related knowledge, attitudes, and communication behaviors: a systematic review and research agenda. <i>J Gen Intern Med</i>. 2017;32:315-324. doi:10.1007/s11606-016-3943-4<br/><br/> 4. Eden KB, Ivlev I, Bensching KL, et al. Use of an online breast cancer risk assessment and patient decision aid in primary care practices. <i>J Womens Health (Larchmt)</i>. 2020;29:763-769. doi: 10.1089/jwh.2019.8143<br/><br/> 5. Kleibl Z, Kristensen VN. Women at high risk of breast cancer: molecular characteristics, clinical presentation and management. <i>Breast</i>. 2016;28:136-44. doi: 10.1016/j.breast.2016.05.006<br/><br/> 6. Sciaraffa T, Guido B, Khan SA, et al. Breast cancer risk assessment and management programs: a practical guide. <i>Breast J</i>. 2020;26:1556-1564. doi: 10.1111/tbj.13967<br/><br/> 7. Farkas A, Vanderberg R, Merriam S, et al. Breast cancer chemoprevention: a practical guide for the primary care provider. <i>J Womens Health (Larchmt)</i>. 2020;29:46-56. doi: 10.1089/jwh.2018.7643<br/><br/> 8. McClintock AH, Golob AL, Laya MB. Breast cancer risk assessment: a step-wise approach for primary care providers on the front lines of shared decision making. <i>Mayo Clin Proc</i>. 2020;95:1268-1275. doi: 10.1016/j.mayocp.2020.04.017<br/><br/> 9. Catana A, Apostu AP, Antemie RG. Multi gene panel testing for hereditary breast cancer - is it ready to be used? <i>Med Pharm Rep</i>. 2019;92:220-225. doi: 10.15386/mpr-1083<br/><br/> 10. Barke LD, Freivogel ME. Breast cancer risk assessment models and high-risk screening. <i>Radiol Clin North Am</i>. 2017;55:457-474. doi: 10.1016/j.rcl.2016.12.013<br/><br/> 11. Amir E, Freedman OC, Seruga B, et al. Assessing women at high risk of breast cancer: a review of risk assessment models. <i>J Natl Cancer Inst</i>. 2010;102:680-91. doi: 10.1093/jnci/djq088<br/><br/> 12. Kim G, Bahl M. Assessing risk of breast cancer: a review of risk prediction models. <i>J Breast Imaging</i>. 2021;3:144-155. doi: 10.1093/jbi/wbab001<br/><br/> 13. Narod SA. Which genes for hereditary breast cancer? <i>N Engl J Med</i>. 2021;384:471-473. doi: 10.1056/NEJMe2035083<br/><br/> 14. Couch FJ, Shimelis H, Hu C, et al. Associations between cancer predisposition testing panel genes and breast cancer. <i>JAMA Oncol</i>. 2017;3:1190-1196. doi: 10.1001/jamaoncol.2017.0424<br/><br/> 15. Obeid EI, Hall MJ, Daly MB. Multigene panel testing and breast cancer risk: is it time to scale down? <i>JAMA Oncol</i>. 2017;3:1176-1177. doi: 10.1001/jamaoncol.2017.0342<br/><br/> 16. Michailidou K, Lindström S, Dennis J, et al. Association analysis identifies 65 new breast cancer risk loci. <i>Nature</i>. 2017;551:92-94. doi: 10.1038/nature24284<br/><br/> 17. Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. <i>Ann Oncol.</i> 2015;26:1291-1299. doi: 10.1093/annonc/mdv022<br/><br/> 18. Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. <i>N Engl J Med</i>. 2021;384:440-451. doi: 10.1056/NEJMoa2005936<br/><br/> 19. Gao C, Polley EC, Hart SN, et al. Risk of breast cancer among carriers of pathogenic variants in breast cancer predisposition genes varies by polygenic risk score. <i>J Clin Oncol</i>. 2021;39:2564-2573. doi: 10.1200/JCO.20.01992<br/><br/> 20. Gallagher S, Hughes E, Wagner S, et al. Association of a polygenic risk score with breast cancer among women carriers of high- and moderate-risk breast cancer genes. <i>JAMA Netw Open</i>. 2020;3:e208501. doi: 10.1001/jamanetworkopen.2020.8501<br/><br/> 21. Yanes T, Young MA, Meiser B, et al. Clinical applications of polygenic breast cancer risk: a critical review and perspectives of an emerging field. <i>Breast Cancer Res</i>. 2020;22:21. doi: 10.1186/s13058-020-01260-3<br/><br/> 22. Schrager S, Torell E, Ledford K, et al. Managing a woman with <i>BRCA</i> mutations? Shared decision-making is key. <i>J Fam Pract</i>. 2020;69:237-243<br/><br/> 23. US Preventive Services Task Force; Owens DK, Davidson KW, Krist AH, et al. Medication use to reduce risk of breast cancer: US Preventive Services Task Force Recommendation Statement. <i>JAMA</i>. 2019;322:857-867. doi: 10.1001/jama.2019.11885<br/><br/> 24. Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. <i>Ann Surg Oncol</i> 2015;22:3230-3235. doi: 10.1245/s10434-015-4715-9<br/><br/> 25. Britt KL, Cuzick J, Phillips KA. Key steps for effective breast cancer prevention. <i>Nat Rev Cancer</i>. 2020;20:417-436. doi: 10.1038/s41568-020-0266-x<br/><br/> 26. Jatoi I, Kemp Z. Risk-reducing mastectomy. <i>JAMA</i>. 2021;325:1781-1782. doi: 10.1001/jama.2020.22414<br/><br/> 27. Choi Y, Terry MB, Daly MB, et al. Association of risk-reducing salpingo-oophorectomy with breast cancer risk in women with <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants. <span class="Emphasis">JAMA Oncol.</span> 2021;7:585-592. doi:10.1001/jamaoncol.2020.7995</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>bio</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="bio"> <a href="mailto:sbschrag@wisc.edu">sbschrag@wisc.edu</a><br/><br/></p> <p class="disclosure">The authors reported no potential conflict of interest relevant to this article.</p> <p class="DOI">doi: 10.12788/jfp.0421</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>box</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="table"> What is a polygenic risk score for breast cancer? </p> <p>• A polygenic risk score (PRS) is a mathematical method to combine results from a variety of different single nucleotide polymorphisms (SNPs; ie, single base pair variants) into a prediction tool that can estimate a woman’s lifetime risk of breast cancer.<br/><br/>• A PRS may be most accurate in determining risk for women with intermediate pathogenic variants, such as <i>ATM</i> and <i>CHEK2</i>.^19,20 <br/><br/>• PRS has not been studied in non-White women.²¹</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>f1</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="table">algorithm</p> <p class="tabletitle">How to assess breast cancer risk</p> <p class="source">ADH, atypical ductal hyperplasia; BCSC, Breast Cancer Surveillance Consortium; IBIS, International Breast Cancer Intervention Study; LCIS, lobular carcinoma in situ.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>in</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <h2>Practice recommendations</h2> <p><em><span class="dingbat1">❯</span><span class="dingbat1"> </span>Assess breast cancer risk in all women starting at age 35. <span class="dingbat1">❯</span><span class="dingbat1"> </span>Perform enhanced screening in all women with a lifetime risk of breast cancer &gt; 20%. </em></p> <p><em><span class="dingbat1">❯</span><span class="dingbat1"> </span>Discuss chemoprevention for all women at elevated risk for breast cancer. </em></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>t1</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="table"> <table> <tbody> <tr> <td> <p class="table">TABLE 1 <br/><br/></p> <p class="tabletitle">High-risk factors for breast cancer^4-9 </p> </td> </tr> <tr> <td> <ul class="tablebody"> <li>Personal history of chest radiation between ages 10 and 30 </li> <li>Personal history of breast biopsy revealing atypia </li> </ul> <p class="tablebody">¡ Lobular carcinoma in situ <br/><br/>¡ Atypical ductal hyperplasia <br/><br/></p> <ul class="tablebody"> <li>Personal history of breast/ovarian cancer </li> <li>Family member with positive genetic testing (first-degree relative)</li> </ul> </td> </tr> </tbody> </table> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>t2</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p> <span class="dingbat3"> <table> <tbody> <tr> <td> <p class="table">TABLE 2 <br/><br/></p> <p class="tabletitle">Commonly used breast cancer risk assessment tools^10-12</p> </td> </tr> <tr> <td> <p class="tablesub">Model</p> </td> <td> <p class="tablesub">Risk factors included</p> </td> <td> <p class="tablesub">Comments</p> </td> <td> <p class="tablesub">Available at</p> </td> </tr> <tr> <td> <p class="tablebody"><strong>Gail</strong> </p> </td> <td> <ul class="tablebody"> <li>Race/ethnicity</li> <li>First-degree relatives with breast cancer</li> <li>Age at menarche</li> <li>Age at first live birth</li> <li>History of ≥ 1 breast biopsy</li> </ul> </td> <td> <ul class="tablebody"> <li>Designed in 1989</li> <li>Includes DCIS</li> <li>Not accurate for women with previous cancer or chest radiation</li> <li>Does not account for distant family history (ie, second-degree relatives)</li> </ul> </td> <td> <p class="tablebody"> <a href="https://bcrisktool.cancer.gov/">https://bcrisktool.cancer.gov/</a> </p> </td> </tr> <tr> <td> <p class="tablebody"> <strong>Tyrer-Cuzick (IBIS)</strong> </p> </td> <td> <ul class="tablebody"> <li>Race/ethnicity</li> <li>First-, second-degree relatives with breast cancer (includes age of onset)</li> <li>Age at menarche</li> <li>Age at first live birth</li> <li>Hormone therapy</li> <li>BMI</li> <li>History of breast biopsy</li> </ul> </td> <td> <ul class="tablebody"> <li>Includes more extensive family history</li> <li>Includes high-risk ethnicity</li> </ul> </td> <td> <p class="tablebody"> <a href="https://ibis-risk-calculator.magview.com/">https://ibis-risk-calculator.magview.com/</a> </p> </td> </tr> <tr> <td> <p class="tablebody"> <strong>Breast Cancer Surveillance Consortium (BCSC)</strong> </p> </td> <td> <ul class="tablebody"> <li>Race/ethnicity</li> <li>Family history of first-degree relative</li> <li>History of breast biopsies</li> <li>Breast density</li> </ul> </td> <td> <ul class="tablebody">Only model to include breast densityOnly model to include breast density^a</ul> </td> <td> <p class="tablebody"> <a href="https://tools.bcsc-scc.org/BC5yearRisk/intro.htm">https://tools.bcsc-scc.org/BC5yearRisk/intro.htm</a> </p> </td> </tr> <tr> <td> <p class="source">BMI, body mass index; DCIS, ductal carcinoma in situ; IBIS, International Breast Cancer Intervention Study.<br/><br/>^a Breast density is the amount of fibroglandular tissue on mammography; high breast density is a risk factor for breast cancer.</p> </td> </tr> </tbody> </table> </span> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>t3</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="table"> <table> <tbody> <tr> <td> <p class="table"><hl name="362"/>TABLE 3 <br/><br/></p> <p class="tabletitle">Genetic testing criteria⁷ </p> </td> </tr> <tr> <td> <p class="tablebody">• First- or second-degree relative with any of the following:<br/><br/></p> <p class="tablebody">¡ Pancreatic cancer<br/><br/>¡ Metastatic prostate cancer <br/><br/>¡ Male breast cancer <br/><br/>¡ Breast cancer ≤ age 45<br/><br/>¡ ≥ 2 breast cancer primaries in a single individual <br/><br/>¡ ≥ 2 individuals with breast cancer primaries on the same side of the family <br/><br/></p> <p class="tablebody">- At least 1 diagnosed ≤ age 50 <br/><br/></p> <p class="tablebody">• Any relative with ovarian cancer </p> </td> </tr> </tbody> </table> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>t4</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p> <span class="dingbat3"> <table> <tbody> <tr> <td> <p class="table">TABLE 4 <br/><br/></p> <p class="tabletitle">Screening recommendations for women at high risk^8,13,22</p> </td> </tr> <tr> <td> <p class="tablesub">Who</p> </td> <td> <p class="tablesub">Recommendation </p> </td> <td> <p class="tablesub">When</p> </td> <td> <p class="tablesub">Recommended by</p> </td> </tr> <tr> <td> <p class="tablebody">≥ 20% lifetime risk </p> </td> <td> <p class="tablebody">Annual MRI and mammography screening^a </p> </td> <td> <p class="tablebody">Starting 10 years before onset of youngest affected relative <br/><br/>Not before age 30</p> </td> <td> <p class="tablebody">ACR, ACS, NCCN</p> </td> </tr> <tr> <td> <p class="tablebody"><span class="itablebody">BRCA</span><i>1/2</i> mutation carriers </p> </td> <td> <p class="tablebody">Annual MRI and mammography screening^a</p> </td> <td> <p class="tablebody">MRI at age 25 <br/><br/>Mammography at age 30 </p> </td> <td> <p class="tablebody">NCCN</p> </td> </tr> <tr> <td> <p class="source">ACR, American College of Radiology; ACS, American Cancer Society; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network.<br/><br/>^a Staggered every 6 months.</p> </td> </tr> </tbody> </table> </span> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>t5</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p> <span class="dingbat3"> <table> <tbody> <tr> <td> <p class="table">TABLE 5 <br/><br/></p> <p class="tabletitle">Chemoprophylaxis regimens for prevention of breast cancer^7,23,24</p> </td> </tr> <tr> <td> <p class="tablesub">Medication</p> </td> <td> <p class="tablesub">Dosage</p> </td> <td> <p class="tablesub">Eligible women</p> </td> <td> <p class="tablesub">Special considerations</p> </td> </tr> <tr> <td> <p class="tablebody">Tamoxifen (SERM)</p> </td> <td> <p class="tablebody">20 mg/d</p> </td> <td> <p class="tablebody">Premenopausal, postmenopausal</p> </td> <td> <ul class="tablebody"> <li>7 fewer invasive breast cancers (CI, 4-12) per 1000 women over 5 years²³</li> <li>Only medication indicated in premenopausal women</li> <li>Increased risk of VTE (5 extra cases per 1000 women over 5 years),²³ endometrial cancer (4 extra cases per 1000 women over 5 years),²³ and cataracts</li> <li>Menopausal symptoms</li> </ul> </td> </tr> <tr> <td> <p class="tablebody">Raloxifene (SERM)</p> </td> <td> <p class="tablebody">60 mg/d</p> </td> <td> <p class="tablebody">Postmenopausal</p> </td> <td> <ul class="tablebody"> <li>9 fewer invasive breast cancers (CI, 3-15) per 1000 women over 5 years²³</li> <li>Menopausal symptoms </li> <li>Increased risk of VTE (7 extra cases per 1000 women over 5 years)²³</li> </ul> </td> </tr> <tr> <td> <p class="tablebody">Exemestane (AI)</p> </td> <td> <p class="tablebody">25 mg/d</p> </td> <td> <p class="tablebody">Postmenopausal</p> </td> <td> <ul class="tablebody"> <li>16 fewer invasive breast cancers (CI, 8-24) per 1000 women over 5 years²³</li> <li>Up to 50% risk of arthralgias and joint pain⁷</li> <li>Menopausal symptoms</li> <li>Decreased BMD</li> </ul> </td> </tr> <tr> <td> <p class="tablebody">Anastrozole (AI)</p> </td> <td> <p class="tablebody">1 mg/d</p> </td> <td> <p class="tablebody">Postmenopausal</p> </td> <td> <ul class="tablebody"> <li>16 fewer invasive breast cancers (CI, 8-24) per 1000 women over 5 years²³</li> <li>Up to 50% risk of arthralgias and joint pain⁷</li> <li>Menopausal symptoms</li> <li>Decreased BMD</li> </ul> </td> </tr> <tr> <td> <p class="source">AI, aromatase inhibitor; BMD, bone mineral density; SERM, synthetic estrogen reuptake modulator; VTE, venous thromboembolism.</p> </td> </tr> </tbody> </table> </span> </p> </itemContent> </newsItem> </itemSet></root>