Study: Some women with early-stage breast cancer forego chemotherapy


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People with node-negative, ER-positive breast cancer

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A research study named the “Trial Assigning Individualized Options for Treatment” (TAILORx) asked whether chemotherapy is beneficial for women who have mid-range Oncotype DX tumor recurrence scores. This trial — the largest breast cancer treatment trial ever conducted— showed that endocrine therapy alone was as effective as endocrine therapy plus chemotherapy in women with certain types of early-stage breast cancer. The results of this trial are expected to be immediately practice changing (7/20/18)

Contents

At a glance In-depth
Findings     Limitations                                        
Clinical trials Resources and references
Questions for your doctor                                           


STUDY AT A GLANCE

This study is about:

Tailoring breast cancer treatment for women with mid-range Oncotype DX recurrence scores.

Why is this study important?

About half of all breast cancer cases diagnosed in the United States are hormone receptor-positive and node-negative — fed by hormones but not yet spread to the lymph nodes. Adjuvant chemotherapy, chemotherapy after tumor surgery, can reduce risk of recurrence, and the risk of dying from breast cancer in certain patients. But chemotherapy comes with side effects. Being able to determine which patients will or won’t receive benefit from chemotherapy is goal of prognostic tests such as Oncotype DX, Mammoprint, and others. XRAYS reviewed an earlier study by the same group of researchers that supported the clinical validity of Oncotype DX to identify patients who may be safely spared adjuvant chemotherapy. The TAILORx trial is a continuation of this research and asks whether some patients receive unnecessary chemotherapy.

Study findings: 

For women with hormone receptor-positive, HER2-negative, node-negative early-stage breast cancer

  • Overall, women with Oncotype DX recurrence scores of 11-25 did as well on endocrine (hormonal) therapy alone as those given hormonal therapy plus chemotherapy.
  • Women age 50 or younger with Oncotype DX recurrence scores of 16 to 25 who received adjuvant chemotherapy plus hormonal therapy had lower rates of distant recurrence than those who received hormonal therapy alone.

What does this mean for me?

This clinical trial suggests that women with intermediate, mid-range Oncotype DX scores (11-25) do not benefit from adjuvant chemotherapy. However, younger women (50 and under) with higher mid-range scores (16-25) may still benefit from adjuvant chemotherapy. There is a point on the recurrence scale at which chemotherapy is beneficial, but that point is not yet certain. Your doctor may use other factors to decide which treatment is right for you.

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Expert Guidelines

The American Society of Clinical Oncology (ASCO) has published guidelines on the use of different biomarker tests to guide decisions on adjuvant chemoatherapy or hormone therapy in early-stage breast cancer. Among their recommendations. Strength of recommendation is noted in parentheses):

  • OncotypeDx
    • For ER/PR-positive, HER2-negative, node-negative breast cancer, the clinician may use 21-gene recurrence score (21-gene RS; Oncotype DX; Genomic Health, Redwood, CA) to guide decisions for adjuvant systemic chemotherapy. (strong)
    • For ER/PR-positive, HER2-negative, node-positive breast cancer, the clinician should not use the 21-gene RS to guide decisions for adjuvant systemic chemotherapy. (moderate)
    • For patients older than 50 and whose tumors have Oncotype DX recurrence scores <26, and for patients <50 whose tumors have Oncotype DX recurrence scores <16, there is little to no benefit from chemotherapy. Clinicians may offer endocrine therapy alone. (strong)
    • For patients 50 years of age or younger with Oncotype DX recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. (moderate)
    • Patients with Oncotype DX recurrence scores >30 should be considered candidates for chemoendocrine therapy. (strong)
    • Based on Expert Panel consensus, oncologists may offer chemoendocrine therapy to patients with Oncotype DX scores of 26 to 30 (moderate)
  • Mammaprint
    • For patients with ER/PR-positive, HER2-negative, node-negative, breast cancer, the MammaPrint assay may be used in those with high clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good prognosis population with potentially limited chemotherapy benefit. (strong)
    • For patients with ER/PR-positive, HER2-negative, node-negative, breast cancer, the MammaPrint assay should not be used in those with low clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy as women in the low clinical risk category had excellent outcomes and did not appear to benefit from chemotherapy even with a genomic high risk cancer. (strong)
    • For patients with ER/PR-positive, HER2-negative, node-positive, breast cancer, the MammaPrint assay may be used in patients with 1-3 positive nodes and at high clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good prognosis population with potentially limited chemotherapy benefit. However, such patients should be informed that a benefit of chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. (moderate)
    • For patients with ER/PgR-positive, HER2-negative, node-positive, breast cancer, the MammaPrint assay should not be used in patients with 1-3 positive nodes and at low clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy. There are insufficient data on the clinical utility of MammaPrint in this specific patient population (moderate)
  • Prosigna Breast Cancer Prognostic Gene Signature Assay
    • If a patient has ER/PgR-positive, HER2-negative, node-negative breast cancer, the clinician may use the PAM50 risk of recurrence score, in conjunction with other clinicopathologic variables, to guide decisions about adjuvant systemic therapy. (strong)

Additional information on other tumor types and biomarker tests can be found on the ASCO website.

The National Comprehensive Cancer Network (NCCN) has expert-developed guidelines for treating breast cancer. NCCN guidelins for node-negative, ER-positive, Her2-negative breast cancer includes the following recommendations. 

  • For tumors greater than 0.5 cm, strongly consider Oncotype DX. 
    • Adjuvant endocrine therapy is recommended for patients with a recurrence score of less than 26. 
    • Consider adjuvant chemotherapy in women 50 years of age or younger with a recurrence score of 16-25 based on the TAILORx study.
    • Adjuvant endocrine therapy or adjuvant chemotherapy followed by endocrine therapy is recommended for patients with a recurrence score of 26-30.
    • Adjuvant endocrine therapy and adjuvant chemotherapy both recommended for patients with a recurrence score of 31 or higher. 
  • NCCN notes that data are limited with regards to the use of Oncotype in men. Available data suggests that the test provides prognostic information for men. 

NCCN notes that other prognostic tumor tests are available for treatment decision-making. The NCCN guidelines state that the Oncotype Dx 21-gene panel is preferred by the Breast Cancer Panel for node negative breast cancer.  

These guidelins are up-to-date as of 09/28/19.

Questions To Ask Your Health Care Provider

  • What are the side effects of chemotherapy?
  • Will chemotherapy lower my risk for a recurrence?
  • Is it possible that I can be treated with endocrine therapy alone and forego chemotherapy?
  • Are there any other tests that may help determine the best treatment for me?

Open Clinical Trials

The following study is looking at tumor prognostic tests used for decision-making in early-stage breast cancer: 

IN-DEPTH REVIEW OF RESEARCH

Study background:

Oncotype DX is a test to predict whether chemotherapy will benefit a patient with hormone receptor-positive breast cancer. Recurrence scores are based on RNA expression of 21 genes. Recurrence scores range from 0 to 100. Scores of 31 and higher (or 26 and higher in some studies) are associated with chemotherapy benefit. Low recurrence scores (0-10) are associated with a very low risk of recurrence that chemotherapy is not likely to lower any further. While many experts recommend the use of the Oncotype DX tumor test as a predictor of recurrence and to guide chemotherapy recommendations, it was uncertain whether those who had mid-range recurrence scores would benefit from adjuvant chemotherapy.

Researchers of this study wanted to know:

Whether they could further tailor treatment of hormone receptor-positive breast cancer for patients with mid-range Oncotype DX recurrence scores.

Study design:

The phase III, prospective study enrolled women who were 18 to 75 years of age, had hormone receptor-positive, HER2-negative, axillary node-negative breast cancer who met National Comprehensive Cancer Network guidelines for the consideration of adjuvant chemotherapy.

10,273 women registered for the study between October 6, 2010, and April 7, 2016.

There were 9,716 patients with follow-up information who were assigned therapy based on their Oncotype DX recurrence score:

  • 6,711 (69%) had an Oncotype DX recurrence score of 11-25 and were randomly assigned to receive either endocrine therapy alone or endocrine therapy plus chemotherapy.
  • 1,619 (17%) had an Oncotype DX recurrence score of 10 or lower and were assigned to receive endocrine therapy alone.
  • 1,389 (14%) had an Oncotype DX recurrence score of 26 or higher and were assigned to receive chemotherapy plus endocrine therapy.

Median length of endocrine therapy was 5.4 years. The most common chemotherapy regimens among patients were docetaxel-cyclophosphamide (56%) and anthracycline-containing regimens. Hormonal therapies among postmenopausal women most commonly included an aromatase inhibitor (91%) and among premenopausal women either tamoxifen alone or tamoxifen followed by an aromatase inhibitor (78%). Suppression of ovarian function was used in 13% of premenopausal women.

Study findings:  

Results of the TAILORx trial were presented on June 3, 2018, at the annual American Society of Clinical Oncology meeting in Chicago, Illinois and published in the New England Journal of Medicine.

  • In patients with Oncotype DX recurrence scores ranging from 11 to 25, chemotherapy did not improve invasive disease-free survival (iDFS) when added to adjuvant endocrine therapy.
    • For endocrine therapy alone versus endocrine therapy plus chemotherapy:
      • Nine-year iDFS rates were 83.3% and 84.3%.
      • Freedom from recurrence of breast cancer at a distant site were 92.2% and 92.9%.
      • Freedom from recurrence of breast cancer at a distant or local-regional site were 93.9% and 93.8%.
      • Overall survival was 93.9% and 93.8% respectively.
  • Women with Oncotype DX scores of 26 or higher had poorer outcomes with higher with higher even rates despite the addition of chemotherapy to endocrine therapy.
  • Younger women (50 years or under) with a recurrence score of 16 to 25 saw some benefit with adjuvant chemotherapy (slightly less than half of women in this age group had scores in this range).
    • Women 50 or younger with recurrence scores of 16 to 20 who had adjuvant chemotherapy had fewer distant recurrences.
    • Women 50 or younger with recurrence scores of 21 to 25 who received adjuvant chemotherapy had 7% fewer distant recurrences.

Limitations:

While chemotherapy had some benefit for women 50 years of age or younger with recurrence scores of 16 to 25, it is not clear why. It is possible that this observation is due a lowering of estrogen from chemo-induced menopause, but the researchers did not collect data on that. It remains unclear whether similar benefits could be achieved with ovarian suppression coupled with an aromatase inhibitor for these women.

Conclusions:

In the early 2000s, most patients with breast cancer who were hormone receptor-positive and node-negative received chemotherapy, but most did not benefit from it. The results of the TAILORx trail, the largest breast cancer treatment trial ever conducted, suggest that the Oncotype DX tumor test could identify up to 85% of women with early breast cancer who can forego adjuvant chemotherapy, especially women older than 50 with a recurrence score of 25 or less and women 50 years of age or younger with a recurrence score of 15 or less. This trial, as well as other smaller trials, have generated new data that can guide adjuvant chemotherapy use for patients.  More studies are needed to clarify those women who need more of some therapies and less of other therapies.

Posted 7/20/18

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