509 - Breast Cancer Screening, Lipids in CCD, Being Ready
From the Literature
1) Breast CA screening Two-fer: Better Sensitivity and Overdiagnosis
Last week we discussed the draft US Preventive Services Task Force breast cancer screening recommendation last week. This week – two quick studies that provide some additional context for that recommendation.
First study: A Cochrane review looks at adding ultrasound routinely to mammograms for breast cancer screening. The review, done with the usual stringent Cochrane methods, found 8 studies (only 1 randomized controlled trial, RCT) involving over 220,000 patients. The studies used either digital mammography or digital breast tomosynthesis to which ultrasound was added in one of the groups. No study actually examined the effect of adding ultrasound on breast cancer mortality or all-cause mortality. The single RCT (a Japanese study with over 72,000 subjects) showed that adding an ultrasound detected more breast cancers (5 versus 3 per 1000, RR 1.54, 95% CI 1.22 to 1.94, NNS~500). However, more false positives also occurred (37 additional per 1000 women without cancer, RR 1.43, 95% CI 1.37 to 1.50, NNH~27) resulting in biopsies or other workups. The cohort studies were consistent with these findings.
Subgroup analysis of over 19,000 women with dense breasts in the RCT also showed greater detection of cancer (3 per 1000 additional, RR 1.65, 95% CI 1.0 to 2.7, NNS~333), with a higher risk of false positives in the cancer negative women (14.6% vs. 8.3%; RR 1.76, 95% CI 1.58 to 1.96, NNH~16).
Second study: The issue of overdiagnosis is an important one to understand when evaluating screening programs. This is different from a false positive, which is an error sorting positive and negative test results correctly; overdiagnosis is a problem with a too-inclusive definition of disease. This happens mostly in cancer screening when the disease looks like cancer microscopically but behaves in the patient in a much less aggressive manner and would not cause symptoms in the patient’s lifetime. This is thought to happen with ductal carcinoma in situ (DCIS). DCIS, on average, does not cause the same rate of morbidity and mortality as other breast cancers, but is often treated aggressively anyway. In older women, this problem is especially tricky because of the variation in life expectancy that comes with older age – a lower life expectancy limits the value of screening. The authors of a retrospective cohort study using some of the same data that the US Preventive Services Task Force uses in its statistical modeling, examining the risk of breast cancer diagnosis in screened vs. unscreened women as well as breast cancer mortality. There was an increasing rate of overdiagnosis with advancing age – from 31% of positive screenings resulting in overdiagnosis (ages 70-74) to 47% (ages 75-84) to 54% (age 85+), and no increase in breast cancer mortality. The absolute risks in each of these groups were in the single digit percents (6.1% down to 1.3%).
As is often the case in medicine, there is a downside to too much screening. Screening programs will never prevent 100% of cancers. Expanding screening by increasing age ranges, getting more sensitive tests, and adopting a too-broad definition of disease can all cause harm by causing anxiety over false positives, increase risks from further testing and even causing overtreatment while resulting less benefit. Look to groups (like the USPSTF) who balance the benefits and harms of screening and be critical of recommendations that don’t present information about potential harms. If we want to improve the benefits of screening, we should make sure it is offered to all the patients for whom it is currently indicated before looking to greater detection methods and expanded age ranges.
· Glechner A, Wagner G, Mitus JW, et al. Mammography in combination with breast ultrasonography versus mammography for breast cancer screening in women at average risk. Cochrane Database Syst Rev. 2023;3(3):CD009632. Link
· Richman IB, Long JB, Soulos PR, Wang SY, Gross CP. Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States. Ann Intern Med. Published online August 8, 2023:M23-0133. Link
From the American College of Cardiology/American Heart Association
2) Updated Lipid Management in Chronic Coronary Disease (CCD)
In last week's Take 3, we reviewed the updated guideline from the American Heart Association (AHA), the American College of Cardiology (ACC), and other specialty societies, for the evidence-based and patient-centered approach to management of chronic coronary disease (CCD), incorporating the principles of shared decision-making, social determinants of health (SDOH), and team-based care. CCD is defined as a heterogeneous group of conditions that includes obstructive and nonobstructive CAD with or without previous MI (MI) or revascularization, ischemic heart disease diagnosed only by noninvasive testing, and chronic angina syndromes with varying underlying causes.
In part 2 of this Pointer, the focus is specifically on the updated recommendations for lipid management in persons with CCD. Each recommendation has both a Class (Strength) of Recommendation (COR) and Level of Evidence (LOE) indicated as (COR/LOE):
1) High-intensity statin therapy is recommended with the aim of achieving a ≥50% reduction in LDL-C levels to reduce the risk of major adverse cardiac events (MACE). (Strong/A)
2) In patients in whom high-intensity statin therapy is contraindicated or not tolerated,
moderate-intensity statin therapy is recommended with the aim of achieving a 30% to 49% reduction in LDL-C levels to reduce the risk of MACE. (1/A)
3) Adherence to changes in lifestyle and effects of lipid-lowering medication should be assessed by measurement of fasting lipids in 4 to 12 weeks after statin initiation or dose adjustment and then every 3 to 12 months thereafter based on need to assess response or adherence to therapy. (Strong/A)
4) The use of generic formulations of maximally tolerated statin therapy is projected to be cost saving. (High Value/B-NR)
5) In patients with CCD who are judged to be at very high risk (based on any of the following: age > 65, DM, HTN, CKD, tobacco use, HLD, Hx HF) and on maximally tolerated statin therapy with an LDL-C level ≥70 mg/dL, ezetimibe can be beneficial to further reduce the risk of MACE. (Moderate/B-R)
6) In patients with CCD, addition of generic ezetimibe to maximally tolerated statin therapy in appropriately selected high risk patients is projected to be of high economic value at US prices. (High Value/B-NR)
7) In patients with CCD who are judged to be at very high risk (see above) and who have an LDL-C level ≥70 mg/dL, or a non–high-density lipoprotein cholesterol level ≥100 mg/dL, on maximally tolerated statin and ezetimibe, a PCSK9 monoclonal antibody can be beneficial to further reduce the risk of MACE. (Moderate/A)
8) In patients with CCD who are very high risk, the use of PCSK9 monoclonal antibodies is projected to be of uncertain economic value at US prices. (Value Uncertain/B-NR)
9) In patients with CCD on maximally tolerated statin therapy with an LDL-C level <100 mg/dL and a persistent fasting triglyceride level of 150 to 499 mg/dL after addressing secondary causes, icosapent ethyl may be considered to further reduce the risk of MACE and cardiovascular death. (Weak/B-NR)
10) In patients with CCD who are not at very high risk and on maximally tolerated statin
therapy with an LDL-C level ≥70 mg/dL, it may be reasonable to add ezetimibe to further reduce the risk of MACE. (Weak/B-R)
11) In patients with CCD on maximally tolerated statin therapy who have an LDL-C level ≥70 mg/dL and in whom ezetimibe and PCSK9 monoclonal antibody are deemed insufficient or not tolerated, it may be reasonable to add bempedoic acid or inclisiran in place of PCSK9 monoclonal antibody) to further reduce LDL-C levels. (Weak/B-R)
12) In patients with CCD receiving statin therapy, adding niacin, fenofibrate, or dietary supplements containing omega-3 fatty acids are not beneficial in reducing cardiovascular risk. (No Benefit/B-R)
What compelled me to go into more depth highlighting this aspect of the guideline was the recommendation regarding LDL targets in general for CCD (>50% reduction in LDL) and for those with CCD at very high risk (LDL target <70). In looking at the definition of high risk in the guideline, most of my patients with CCD would also be considered very high risk. Additionally, the recommendation regarding the use of ezetimibe as a “high value” intervention is more compelling than with past guidelines, and this is something I will likely look to use more often for the subpopulation of patients not meeting the LDL target with a high intensity statin alone.
· Virani S, et al. 2023 AHA/ACC Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. Published ahead of print 20 July 2023. Link
From PeerRxMed: The Great Recalibration” (Part 3):
3) You Reading This, Be Ready
“If everything is important, then nothing is important.” Patrick Lencioni, author and leadership consultant
From PeerRxMed: The Great Recalibration” (Part 3):
One of the things I’ve learned over the years is that “words matter.” This is not only true in our communication with others, but also and perhaps more importantly, in the dialogues we have within ourselves. After my blog last week, one of our PeerRx colleagues asked me what I thought the difference was between “reprioritization”, which I’ve written about in the past, and “recalibration” which I’ve been writing about over the past few weeks.
Prioritization for me involves an explicit alignment of attention around the “Big Rocks” in life, and therefore where one focuses the bulk of their time, energy, and attention. The process of reprioritization becomes necessary when there is a sense that something is “broken” and therefore frequently requires a significant shift or “fix”. For many colleagues over the past few years, doing so has involved de-emphasizing their professional life for the sake of their life beyond medicine.
“Recalibration,” on the other hand, is more about “fine-tuning.” Professionally, it involves determining “degrees” of importance and requires making continual adjustments of our time and attention so that we don’t get distracted by less important things. What makes recalibration challenging for many is the need to say “no” regularly.
So, why my present need to recalibrate? While I continue to greatly enjoy my work and feel no need to “reprioritize,” I recognize if I am unwilling to regularly discern the various levels of importance of the daily demands for my attention and allocate my time and energy accordingly, I will be constantly pulled in too many different directions and therefore be left feeling scattered … ungrounded … ineffective … or just plain weary. .
It is during such times that I find the wisdom contained in the word play of a poem can shake me out of my scatteredness and weariness as I allow the flow of images to help me regain perspective and recalibrate what really matters to me, and for me … right now.
With the poem below, they did. Perhaps they will for you as well ….
You Reading This, Be Ready by William Stafford
Starting here, what do you want to remember?
How sunlight creeps along a shining floor?
What scent of old wood hovers, what softened
sound from outside fills the air?
Will you ever bring a better gift for the world
than the breathing respect that you carry
wherever you go right now? Are you waiting
for time to show you some better thoughts?
When you turn around, starting here, lift this
new glimpse that you found; carry into evening
all that you want from this day. This interval you spent
reading or hearing this, keep it for life –
What can anyone give you greater than now,
starting here, right in this room, when you turn around?
Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.
Mark and John