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Annals for Educators - 16 February 2016Annals for Educators - 16 February 2016 FREE

Darren B. Taichman, MD, PhD
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From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Associate Dean of Graduate Medical Education and Affiliations, Thomas Jefferson University.


Ann Intern Med. 2016;164(4):ED4. doi:10.7326/AFED201602160
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(Mobile users can access the video here.)

Story Slams celebrate storytelling by providing an opportunity for participants to share brief stories with an audience. In the tradition of the popular Annals feature, physicians—both young and old—shared poignant and inspiring moments at Annals On Being a Doctor Story Slam.

Use this feature to:

  • Watch this short video in which Dr. Faith Fitzgerald shares a lesson of empathy.

  • Do you or other physicians at your center recall the early days of the HIV epidemic, when AIDS patients were feared and even shunned by the public and even health care providers? Share these memories with your learners.

  • How have things changed?

  • Ask your learners if certain patients seem to have been abandoned or less loved than others. Why? Do we fear them? Do we blame them for their illness? What might it say about us if we lack compassion for certain patients? What can we do?

  • Can empathy be taught?

This study simulated mammography screening trials done before chemotherapy was used to treat breast cancer. It assesses the relative and absolute changes in mortality associated with treatments reflecting practice in 1999 and more current treatments to test whether the benefit of screening has changed.

Use this study to:

  • Start a teaching session with a multiple choice question. We've provided two below.

  • Ask your learners to list the criteria required for screening to be appropriate for a condition.

  • Why might improvements in the effectiveness of treatment for later-stage disease alter the benefit of a screening program? How might the balance of benefits and harms change?

  • This study found that advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. Why is it important to try to update assessments of whether screening remains beneficial in the setting of modern therapies?

These studies were conducted to inform the U.S. Preventive Services Task Force's recommendations for breast cancer screening in average-risk women. The first examines the radiation-induced breast cancer incidence and mortality that might occur with annual or biennial digital mammography screening. The next evaluates the benefits and harms of 8 screening strategies, which differ by starting age and interval. A third study uses registry data to assess the rates of false-positive and false-negative results from mammography. The 2 reviews summarize evidence from randomized trials and observational studies about the effectiveness and harms of screening in average-risk women.

Use these studies to:

  • Assign 5 groups to each succinctly summarize the findings of just one report. Tell your learners to briefly list the benefits and harms reported and how confident the data are.

  • As each group summarizes its paper, list the key findings on the board, with emphasis on reported benefits and harms according to patients' ages as well as the quality of the available information.

  • Ask your learners what overdiagnosis and overtreatment are.

  • After summarizing, ask each group to formulate its own recommendations regarding screening mammography for average-risk women in each of several age groups.

This guideline from the USPSTF provides recommendations for mammography screening among average-risk women aged ≥40 years.

Use this guideline to:

  • Have your learners read the clinical practice guideline.

  • Ask them if they agree with the Task Force's recommendations. In what ways do they agree or disagree with the recommendations your learners made after hearing summaries of the evidence in the activity above?

  • Have your learners role-play “shared decision making” with women aged 40 to 49 years. What questions might they ask a 40-year-old average-risk woman who wonders if she should undergo mammography screening? How would your learners explain the potential risks and benefits?

  • Ask your learners why breast cancer screening is so contentious. What role do they think lawmakers should play in regulating what screening services are covered by insurance? Use the accompanying editorials by Siu et al and Laine et al to help frame your discussion.

A 51-year-old woman undergoes a follow-up evaluation. The patient recently required surgery for stage I cancer of the right breast confirmed as a grade 3 invasive ductal carcinoma that was estrogen receptor negative, progesterone receptor negative, and HER2 negative. Sentinel lymph nodes were negative. The patient currently states that she feels well. Medical history is otherwise unremarkable, and she is perimenopausal.

On physical examination, vital signs are normal. Healed incisions of the right breast and right axilla are present. There are no masses in either breast and no lymphadenopathy. The remainder of the examination is unremarkable.

Which of the following is the most appropriate next step in management?

A. Anastrozole

B. Anthracycline-based chemotherapy

C. Autologous hematopoietic stem cell transplantation

D. Bevacizumab

Correct Answer

B. Anthracycline-based chemotherapy

Educational Objective

Treat early-stage triple-negative breast cancer with adjuvant chemotherapy.

Critique

Anthracycline-based chemotherapy is the most appropriate treatment. Although this patient has a stage I cancer (measuring 2 cm or less and lymph node negative), it is a high-grade, triple-negative tumor (negative for estrogen receptor, progesterone receptor, and HER2 amplification), and she is at high risk for systemic recurrence. In patients with triple-negative cancers that are 0.6 cm or greater in size, adjuvant chemotherapy, typically anthracycline-based chemotherapy, is recommended if there are no medical contraindications. Chemotherapy is the mainstay of treatment for triple-negative breast cancers, both when used as adjuvant therapy and when used for more advanced cancers. Based on retrospective analysis, adding a taxane agent to adjuvant anthracycline-based chemotherapy is of greater benefit in patients with hormone receptor–negative cancers than in patients with hormone receptor–positive cancers.

Triple-negative cancers constitute about 15% of breast cancers and are usually of high grade. They occur more frequently in young black and Hispanic women than in other ethnic groups. Patients with triple-negative cancers have a higher risk of BRCA1/2 mutations, and BRCA1/2 genetic testing is recommended for women diagnosed with triple-negative breast cancers before age 60 years. Most breast cancers in women with BRCA1 mutations are triple negative.

Antiestrogen therapies such as anastrozole are not effective in hormone receptor–negative cancers and would not be used in this patient's treatment regimen.

Autologous bone marrow transplantation is not used as adjuvant treatment for breast cancer. Clinical trials on its use in both the adjuvant setting and the metastatic setting showed no improvement in survival compared to treatment with standard therapy and its use in breast cancer has been discontinued.

Epidermal growth factor receptor–targeted therapy with bevacizumab has not been found to improve disease survival or overall survival when added to adjuvant chemotherapy for patients with triple-negative breast cancers.

Key Point

Adjuvant chemotherapy, typically anthracycline-based chemotherapy, is recommended for patients with triple-negative breast cancers who have no medical contraindications to this regimen.

Bibliography

Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010 Nov 11;363(20):1938-48.

A 43-year-old woman undergoes follow-up evaluation following a recent diagnosis of estrogen receptor–positive, progesterone receptor–positive, HER2-negative, grade 2 invasive ductal carcinoma of the left breast. The patient was treated with surgery, adjuvant chemotherapy, and radiation therapy. This is her first postradiation visit. She currently takes no medications. She is premenopausal.

On physical examination, vital signs are normal. Well-healed incisions of the left breast and left axilla are present. There is no lymphadenopathy and no right breast masses. The remainder of the examination is unremarkable.

Results of a complete blood count and serum chemistry panel are normal.

Which of the following is the most appropriate therapy?

A. Exemestane alone

B. Tamoxifen alone

C. Maintenance chemotherapy with oral capecitabine

D. No additional adjuvant therapy

Correct Answer

B. Tamoxifen alone

Educational Objective

Treat a premenopausal patient who has completed breast cancer therapy with antiestrogen therapy.

Critique

This patient, who has completed breast surgery, adjuvant chemotherapy, and primary breast radiation, should now be started on antiestrogen therapy. Tamoxifen has been the standard treatment in premenopausal women. As her breast cancer is estrogen receptor positive, adjuvant antiestrogen therapy will reduce her risk of distant recurrence by 40% to 50%. For premenopausal women with hormone receptor–positive early-stage breast cancer, tamoxifen should be used for at least 5 years—preferably 10 years based on the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and Adjuvant Tamoxifen Treatment Offers More (aTTom) trials.

Exemestane is an aromatase inhibitor that blocks peripheral conversion of androgens to estrogens. Aromatase inhibitors are therefore used only in postmenopausal women in whom the primary source of estrogen is peripheral conversion of adrenal androgens; therapy with exemestane alone would therefore not be appropriate in the woman with residual ovarian function. However, exemestane has recently been compared with tamoxifen in conjunction with ovarian suppression in premenopausal women. The Tamoxifen and Exemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT) trials have shown improved disease-free survival at 5 years for exemestane with ovarian suppression compared to tamoxifen with ovarian suppression, and this is now an option that can be discussed with premenopausal patients, particularly those at high risk of recurrence. There is at present no difference in breast cancer mortality between these two treatments and the toxicity analysis of these treatments with ovarian suppression compared to tamoxifen alone has not yet been done.

There is no evidence that maintenance chemotherapy is effective in early stage breast cancer and it has not been used outside of a clinical trial.

Without antiestrogen adjuvant therapy, the patient's risk of distant recurrence will increase. As above, antiestrogen therapy reduces the risk of breast cancer distant recurrence by 40 to 50% and also decreases the risk of contralateral breast cancers by 50%. Its use should be recommended in this patient with hormone receptor–positive early-stage breast cancer.

Key Point

The recommended adjuvant endocrine therapy following breast cancer treatment for a premenopausal patient is tamoxifen for at least 5—preferably 10—years.

Bibliography

Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 2014 Jul 20;32(21):2255-69.

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