FDA Finalizes New Mammography Dense Breast Notification Rule

SUMMARY:

The FDA has updated the mammography regulations and now requires that mammography facilities notify patients about the density of their breasts. The amendments incorporate language that specifies how breast density can influence the accuracy of mammography in addition to recommending a discussion with their healthcare professional. The rule goes into effect September 10, 2024. Currently, the ACOG committee opinion states unequivocally that healthcare professionals comply with all laws, although evidence is lacking as to clinical utility and improved outcomes with additional screening and testing.

Summary of Results to be Provided to Patients (FDA Rule)

Non-Dense Breast

Breast tissue can be either dense or not dense

Dense tissue makes it harder to find breast cancer on a mammogram and also raises the risk of developing breast cancer

Your breast tissue is not dense

Talk to your healthcare provider about breast density, risks for breast cancer, and your individual situation

Dense Breast

Breast tissue can be either dense or not dense

Dense tissue makes it harder to find breast cancer on a mammogram and also raises the risk of developing breast cancer

Your breast tissue is dense

In some people with dense tissue, other imaging tests in addition to a mammogram may help find cancers

Talk to your healthcare provider about breast density, risks for breast cancer, and your individual situation

ACOG

• The current ACOG Practice Advisory States

While ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in individuals with dense breasts who are asymptomatic and have no additional risk factors, ACOG recommends that clinicians comply with the new FDA rule and any state laws and federal rules that require disclosure of a patient’s breast density as recorded in a mammogram report

BI-RADS Density Categories (for more on BI-RADS classification, see ‘Related ObG Topics’ Below)

• a. Breasts are almost entirely fatty
  • Prevalence: 10%
  • Mammography considered highly sensitive in this setting (88%)
• b. There are scattered areas of fibroglandular density
  • Prevalence: 43%
  • Still sensitive but decreased from category a (82%)
• c. Breasts are heterogeneously dense
  • Prevalence: 39%
  • Small masses may be obscured
  • Sensitivity drops to 69%
• d. Breasts are extremely dense
  • Prevalence: 8%
  • Significantly lowers sensitivity of mammography (62%)

KEY POINTS:

• Dense breast tissue and screening is more common in younger women
  • Accuracy of mammography for the detection of breast cancer is reduced (less sensitive)
  • In women with heterogeneously and extremely dense breasts, digital mammography appears to be superior to film with respect to efficacy
• Breast cancer risk
  • Dense breast tissue (BI-RADS density categories c and d) is associated with increased breast cancer risk
  • BI-RADS c breast cancer risk: 1.2 relative risk compared to average breast density
  • BI-RADS d breast cancer risk: 2.1 relative risk compared to average breast density
• The FDA also has required reporting language that should be provided to the referring healthcare professional that falls into 4 categories

(A) The breasts are almost entirely fatty

(B) There are scattered areas of fibroglandular density

(C) The breasts are heterogeneously dense, which may obscure small masses

(D) The breasts are extremely dense, which lowers the sensitivity of mammography

Learn More – Primary Sources:

FDA Updates Mammography Regulations to Require Reporting of Breast Density Information and Enhance Facility Oversight (2023)

ACOG Committee Opinion 625: Management of Women With Dense Breasts Diagnosed by Mammography

ACOG Practice Advisory: The U.S. Food and Drug Administration Requires Notification of Breast Density in Mammography Reports

ACOG Practice Advisory: Counseling Patients About Breast Cancer Risk and Hormonal Contraception

SUMMARY:

ACOG reaffirmed a practice advisory in 2022 that had initially been in response to a prospective cohort study. The results from the paper by Mørch and colleagues (NEJM, 2017) was based on Danish nationwide registries (see ‘Related ObG Topics’ below) and identified the following

Overall risk of breast cancer in current or recent users compared to women who never used hormonal contraception

• Increased Risk of breast cancer: Relative Risk (RR): 1.20 (95% CI, 1.14 to 1.26)
• Risk increased with duration of use: RR 1.09 (95% CI, 0.96 to 1.23) at < 1 year vs 1.38 (95% CI, 1.26 to 1.51) after > 10 years (P=0.002)
• Risk remains elevated after ≥5 years but not < 5 years

Oral Combined Contraceptives

• Little evidence of major differences between various OCPs after statistical adjustments for multiple testing

Levonorgestrel-releasing intrauterine system (LNG-IUD)

• No significant differences compared to OCPs
• RR of breast cancer was 1.21 (95% CI, 1.11 to 1.33)

Contraceptive implants

• Few breast-cancer events among users of the progestin-only implant and depot medroxyprogesterone acetate

KEY POINTS:

Relative vs Absolute Risk

Absolute risks remain low

• Overall: 1 additional case of invasive breast cancer for every 7,690 women using hormonal contraception
• Women <35 years: 1 additional case of invasive breast cancer for every 50,000 women using hormonal contraception

Benefits of Hormonal Contraceptives

ACOG addresses these benefits clearly in this Practice Advisory

• Non-hormonal benefits (see ‘Related ObG Topics’ below)
  • Decreased risk of ovarian, endometrial, and colon cancer
  • Overall cancer risk may be lower in hormonal contraceptive users despite possibility of small increased breast cancer risk
• Hormonal benefits
  • Maternal mortality rate in the US: 26.4 deaths per 100,000 women (2015)
  • The above risk is twice that of developing invasive breast cancer in the NEJM study

Study Limitations

ACOG highlights the following

• Study confounders not assessed in this study
  • Breastfeeding | alcohol consumption |physical activity
• Study may not be generalizable
  • Only a northern European population was included
• More study required regarding relationship between progestin-only contraceptives and breast cancer risk
  • Study results were inconsistent regarding progestin-only formulations

Counseling recommendations

ACOG supports shared decision making and counseling should include the following

This recent study showed that women who use hormonal birth control methods may have a small increased risk of breast cancer, but the overall risk of breast cancer in hormonal birth control users remains very low

Hormonal birth control is very effective in preventing pregnancy and may lower a women’s overall risk of cancer by providing protection against other types of cancer

There are nonhormonal methods of birth control that are also good options

Women can do things to help lower their risk of breast cancer, like breastfeeding, getting more exercise, and limiting alcohol intake

Learn More – Primary Sources:

Practice Advisory: Hormonal Contraception and Risk of Breast Cancer

Prophylactic Mastectomy and BRCA – Risk Reduction and Guidelines

CLINICAL ACTIONS:

A recent large prospective cohort study (see ‘Related ObG Project’ below) demonstrated that by age 80, the cumulative breast cancer risk for BRCA1 mutation carriers is 72% (95% CI, 65%-79%) and 69% (95% CI, 61%-77%) for BRCA2.  In the context of women with high risk for breast cancer, consider the following:

• Bilateral risk-reducing mastectomy (RRM) is an option for women at high risk for breast cancer
• High-risk includes carriers of deleterious mutations in BRCA1, BRCA2 and other genes associated with high risk of breast cancer such as TP53, PTEN, CH1 or STK11
• Prior to surgery, obtain the following
  • Multidisciplinary consultations with genetic counseling, surgical reconstructive and oncology teams
  • Clinical breast exam
  • Bilateral mammogram if not performed within past 6 months
• If no findings on clinical examination or imaging
  • Women may choose to undergo RRM with or without immediate reconstruction
  • Remove all breast tissue (total mastectomy)
  • Axillary node assessment has limited utility at the time of RRM and only required if cancer identified on pathology
• If patient at risk for occult primary cancer (abnormal imaging or positive family history without MRI imaging available)
  • Sentinel note biopsy may be performed for axillary staging

SYNOPSIS:

There are other management options aside from RRM for women who are at high risk for breast cancer due to pathogenic variants in BRCA and related genes.  Chemoprevention using risk reducing medications such as tamoxifen and raloxifene may be appropriate. Selection of these agents depends on age, race, breast cancer risk and history of hysterectomy. Aromatase inhibitors have also been investigated for use as risk reducing agents.  However, these medications are more effective at preventing ER+ disease which is more highly associated with BRCA2 compared to BRCA1.  Surveillance programs using imaging studies are also available.  Monitoring with MRI is not a preventative strategy but rather an approach that can be used for early detection.

KEY POINTS:

• RRM may not reduce the risk of all-cause mortality but can reduce the risk of breast cancer in BRCA carriers by 85 to 100%
• NCCN and ACOG recommend that RRM be offered to women who are BRCA mutation carriers to reduce the risk of breast cancer
• Shared decision making should include general health and life expectancy

Women at High Risk but Not BRCA Mutation Carriers

According to the National Cancer Institute, other women at high risk for breast cancer, aside from BRCA mutation carriers, who might consider risk reducing mastectomy include (see ‘Primary Sources – Learn More’ below)

Those with a strong family history of breast cancer (such as having a mother, sister, and/or daughter who was diagnosed with bilateral breast cancer or with breast cancer before age 50 years or having multiple family members with breast or ovarian cancer) 

Those with lobular carcinoma in situ (LCIS) plus a family history of breast cancer 

Those who have had radiation therapy to the chest (including the breasts) before the age of 30 years 

Learn More – Primary Sources:

ACOG Practice Bulletin 182: Hereditary Breast and Ovarian Cancer Syndrome

NCCN Guidelines For Detection, Prevention, & Risk Reduction: Breast Cancer Risk Reduction

NCI: Surgery to Reduce the Risk of Breast Cancer

Mammography Guidelines for Average-Risk Women

SUMMARY:

Professional organizations continue to release evidence based guidance on mammography, with ACP the latest to provide updated recommendations. While required frequency and starting age may differ, they all emphasize shared decision making with patients, which entails counseling about uncertainty, risk/benefit and related patient values.

BENEFITS OF MAMMOGRAPHY

• Appears to decrease breast cancer mortality by 15 to 20%
  • Studies demonstrate varying magnitude
  • ACS (RCT data): Relative risk 0.80-0.82
  • Recent data from the Canadian National Breast Screening Study did not show decrease when comparing mammography to controls, perhaps due to more recent improvements in treatments but does not take in to account advances in imaging
• Reduces advanced cancer (although no evidence regarding advanced cancer treatment)
  • USPSTF evidence review in women > 50 years of age: Relative risk 0.62 (95% CI, 0.46 – 0.83)
• May increase life expectancy (ACS systematic review) but could not quantitate

HARMS OF MAMMOGRAPHY

False Positives (additional images and benign biopsies)

• USPSTF review 10 yr cumulative false positive rate
  • Annual: 61% false positive / 7% require biopsy
  • Every 2 years: 42% false positive / 5% require biopsy
• ACS review of the same data
  • Increased risk of false positive with dense breasts among women 40-49
  • Callbacks minimized if prior films available

Anxiety and Distress

• May persist even if follow-up is normal
• Financial concerns as patient may be responsible for paying for additional tests

Discomfort

• USPSTF review identified mammography as being a painful procedure

• Follow-up procedures may also result in pain

Overdiagnosis and Overtreatment

• Overdiagnosis is defined as detecting a cancer that would have remained indolent and not become apparent without screening
• Overtreatment is defined as treatment for an overdiagnosed cancer
• Difficult to discern actual number of overdiagnosed cancers
  • USPSTF review suggests 10.7% – 22.7% based on RCT data
  • 1/8 cancers will be overdiagnosed
• Inclusion of Ductal Carcinoma in Situ may impact data
• Other organizations such as ACS make the point that certain assumptions may not be verifiable in addition to bias in methodology and design

Radiation

• USPSTF using modelling but not direct studies of radiation exposure estimates 2 per 100,000 deaths among women 50-59 yrs due to mammography screening
• Other models in women 40-74 yrs suggest 125 cases of breast cancer and 25 cancer deaths due to radiation exposure, but 986 cancer deaths prevented

PROFESSIONAL GUIDELINES:

ACOG

• Start Age
  • Recommend at age 50
  • Offer from age 40 (shared decision making)
• Screening Interval
  • Every 1 or 2 years (shared decision making)
• Stop Age
  • Age 75
  • > 75 shared decision making including overall health and longevity

USPSTF

• Start Age
  • Recommend at 50 years | Consider 40 years if patient desires

• Screening Interval: Every 2 years until 74 years
• Stop Age
  • ≥ 75 years:  Insufficient evidence to recommend for/against

ACS

• Start Age
  • Recommend at age 45 years | Consider 40 years if patient desires

• Screening Interval
  • 45 – 50 years: annual
  • ≥55 years: Every 2 years or can choose annual
• Stop Age
  • Continue if good health and life expectancy >10 years

ACR

• Start Age
  • Recommend at 40 years
• Screening Interval: Annual
• Stop Age
  • “Screening should continue past age 74 without an upper age limit, unless severe comorbidities limit life expectancy or ability to accept treatment.“

Note: ACR updated guidelines to include transgender patients stating “Annual screening at age 40 is recommended for transfeminine (male-to-female) patients who have used hormones for ≥5 years, as well as for transmasculine (female-to-male) patients who have not had mastectomy” 

ACP

• Start Age
  • • Recommended at 50 years
  • 40-49 years: Discuss risks vs benefits and patient preference (“potential harms outweigh the benefits for most women” in this age bracket )
• Screening Interval: Every 2 years
• Stop Age
  • Screening not recommended for women ≥75
  • Life expectancy ≤10 years

AAFP

• Start Age

• • Recommend at 50 years
• Screening Interval
  • Every 2 years
• Stop Age
  • ≥ 75 years:  Insufficient evidence to recommend for/against

NCCN

• Start Age
  • Recommend at 40 years
• Screening Interval: Annual
• Stop Age
  • Upper age limit not yet established
• Consider comorbidities that may impact life expectancy (≤10 years)

Canadian Task Force on Preventative Healthcare

• Start Age
  • Recommend not to screen women 40 to 49 years (conditional recommendation; low-certainty evidence)
• Screening Interval

• • Every 2 to 3 years
  • 50 to 69 years: “Conditional on the relative value that a woman places on possible benefits and harms from screening (conditional recommendation; very low-certainty evidence)”
  • 50 to 59 years: 1333 women is the number needed to screen (NNS) to prevent one death from breast cancer (95% CI, 909 to 2857)
  • 60-69 years: NNS is 1087 (95% CI, 741 to 2325)
  • 70-74 years: NNS is 645 (95% CI, 441 to 1389)
• Stop Age
  • No evidence found regarding harms vs benefits of screening ≥75 years

Note: The Canadian Task Force did not make any significant change from the previous guideline, however certainty of evidence – now ‘very low- to low-certainty’ was downgraded based on serious concerns of previous study bias

American Society of Breast Surgeons

• Start Age
  • Non-dense breasts (A and B density): 3D preferred modality | Age 40 | No need for supplemental imaging
  • Dense breasts (C and D density): 3D preferred modality | Age 40 | Consider supplemental imaging
• Screening Interval
  • Annual
• Stop Age
  • When life expectancy is <10 years

ADDITIONAL KEY POINTS: 

• Clinical Breast Examination (CBE)
  • ACOG & NCCN: Offer every 1 to 3 years for women 25 to 39 years and annually for ≥ 40 years
  • USPSTF & AAFP: Insufficient evidence to recommend for or against
  • ACS, ACP & Canadian Task Force on Preventative Healthcare: Not recommended
  • WHO: CBE may be of benefit for women age 50 to 69 years with poor access to healthcare resources 
• Most professional organizations find insufficient evidence to recommend adjunctive screening using breast ultrasonography, MRI, Digital Breast Tomosynthesis, or other method in the setting of a normal mammogram and no other risk factors

Learn More – Primary Sources:

ACOG Practice Bulletin 179: Breast Cancer Risk Assessment and Screening in Average-Risk Women

Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement

Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial

Canadian Task Force: Recommendations on screening for breast cancer in women aged 40–74 years who are not at increased risk for breast cancer

Breast Cancer Screening Recommendations Inclusive of All Women at Average Risk: Update from the ACR and Society of Breast Imaging

Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society

Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians

AAFP: Summary of Recommendations for Clinical Preventative Services

NCCN Guidelines: Breast Cancer Screening and Diagnosis

ASBrS: Position Statement on Screening Mammography

Radiation-Induced Breast Cancer Incidence and Mortality from Digital Mammography Screening: A Modeling Study 

WHO position paper on mammography screening