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Weighing the options for adjuvant therapy after lumpectomy
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A 50-year-old premenopausal woman came to the oncology clinic for the recommendations of adjuvant therapy after lumpectomy. She initially palpated a small lump in her right breast about three months prior. She was promptly sent by her gynecologist for a mammogram that showed a 1 cm mass in the upper outer quadrant of the right breast. An ultrasound confirmed the presence of a 1.2 cm mass at the same area. The patient denied any pain in the right breast and nipple discharge. She had menarche at age 13 and has never been pregnant. Her family history was unremarkable. A core biopsy showed poorly differentiated infiltrating ductal cancer with 90% expression of estrogen and progesterone receptors and 1+ HER2/neu by immunohistochemistry. She underwent lumpectomy with sentinel lymph node dissection and was found to have T1c (1.4 cm) N0Mx disease. She had an uncomplicated postoperative course and the surgical site was well healed.
How would you manage her case?
A) Offer four cycles of doxorubicin and cyclophosphamide followed by radiation and hormonal therapy.
B) Offer doxorubicin and cyclophosphamide followed by four cycles of paclitaxel, radiation and hormonal therapy.
C) Offer Oncotype Dx assay (or TAILORx trial) before deciding about chemotherapy.
D) Offer radiation now followed by hormonal therapy.
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Source: W Razaq |
CASE DISCUSSION
Breast cancer is the most common cancer in women and is the second most common cause of cancer death. A variety of factors influence the treatment of breast cancer and the most important are the involvement of axillary lymph nodes, tumor size, expression of hormonal receptors or HER2/neu, and a woman’s age and menopausal status. Surgical as well as adjuvant therapy for early stage breast cancer has significantly improved in the past decade resulting in extraordinary progress in our understanding of the disease and in new, more efficient and less toxic treatments.
The body of knowledge about adjuvant chemotherapy has emerged from the serial Oxford updates and many large randomized trials. Combination chemotherapy is superior to single agent chemotherapy in adjuvant settings and it has been shown that anthracycline-containing regimens are slightly but significantly superior to traditional chemotherapy (cyclophosphamide, methotrexate and 5-FU).
Figure 2: Schema TAILORx TrialSource: W Razaq
In patients with early stage node-negative disease, chemotherapy is not indicated if the tumor is less than 0.5 cm in size, associated with good risk features, ie, low nuclear grade, ER/PR-positive and HER2/neu-negative. Patients with invasive ductal or lobular carcinomas with tumors between 0.6 cm and 1.0 cm may require chemotherapy if associated with bad risk features, eg, HER2/neu-positive, high nuclear grade, angiolymphatic invasion and negative hormonal receptors. Decisions aids such as adjuvant online, decision boards and other tools are usually helpful in assessing the benefits of adjuvant chemotherapy in these patients, but predicting who is going to benefit from adjuvant therapy is an inexact science. This has generated a lot of interest in the notion of developing tools that may predict the recurrence score and benefit from adjuvant therapy more accurately. Several multigene models have been developed during the past five years and some of them were specifically designed for predicting outcomes by performing gene expression profiles of relapsing and non-relapsing tumors. These are a 70-gene profile, a 76-gene profile, a 21-gene profile, a two-gene profile and a 97-genomic grade profile.
Researchers from several small studies have suggested that the 21-gene Oncotype Dx (Genomic Health) recurrence score may provide information that can alter the therapeutic decisions about 25% of the time. Liang et al published a retrospective study of 260 patients with estrogen -positive, lymph-node and HER2/neu-negative invasive breast cancer who had a recurrence score conducted at a single institution. Forty-six percent had low (<18), 36% had intermediate (18 to 31), and 18% had a high recurrence score. Less than 5% of patients (4 of 120) with a recurrence score of 18 or less were treated with chemotherapy. Based on these results the researchers concluded that recurrence score reduced the frequency of chemotherapy given.
Later, Erb et al also observed the same findings after reviewing the recurrence scores of 325 patients. Taken together, these findings confirm those of other reports that the use of this assay results in a treatment sparing decision regarding adjuvant chemotherapy in about 25% of patients.
A currently on-going prospective trial (TAILORx) has been sponsored by the NCI to evaluate and treat more than 10,000 women with estrogen-positive, HER2/neu- and lymph-node negative tumors based on their recurrence scores. The schema of the trial is shown in figure 2.
We also enrolled our patient in the TAILORx trial and her recurrence was determined to be 18 (intermediate risk); she was randomly assigned to the hormonal arm.
By integrating molecular diagnostic tests into the clinical decision-making process, we will be able to make more informed treatment decisions and chemotherapy may be avoided in women who are likely to be cured with hormonal therapy alone.
Wajeeha Razaq, MD, is a third-year HemOnc Fellow at St. Luke’s Roosevelt Hospital Center in New York and is a HemOnc Today Editorial Board member.
For more information:
- Liang. A retrospective analysis of the impact of Oncotype DX low recurrence score results on treatment decisions in a single academic breast cancer center. Breast Cancer Res Treat. 2007;106:S105.
- Erb. Evaluation of practice patterns in the treatment of node-negative, hormone-receptor positive breast cancer patients with the use of the Oncotype DX assay at the University of Pennsylvania. Breast Cancer Res Treat. 2007;106:S154.