BREAST CANCER
Benefit for Neoadjuvant Chemotherapy Seen in Very Young Patients With Triple-Negative and Luminal-Like Breast Cancer By Alice Goodman
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oung women with triple-negative and luminal-type breast cancer were more likely to respond to neoadjuvant chemotherapy than were older women with these cancers, and improved outcomes were observed for young women with luminal-A–like tumors who achieved a pathologic complete response (pCR) versus those who did not. The study suggests that neoadjuvant chemotherapy is beneficial for young women with triple-negative and luminal-type breast cancer, even those with favorable biological features that include hormone receptor positivity (HR+) and human epidermal growth factor 2–negative (HER2–) disease. “Breast cancer is less common in women age 35 or younger, and some data suggest that these younger patients
have a worse prognosis. This is not only because they tend to have more aggressive breast cancers, but because tumors that arise in younger women
leagues reported at the CTRC-AACR San Antonio Breast Cancer Symposium included a total of 8949 women from 8 German studies. All women had oper-
“Breast cancer is less common in women age 35 or younger, and some data suggest that these younger patients have a worse prognosis.” Sibylle Loibl, MD, PhD
appear to have different biological features,” stated Sibylle Loibl, MD, PhD, associate professor at the University of Frankfurt, Germany. The meta-analysis that Loibl and col-
able or locally advanced nonmetastatic breast cancer and received neoadjuvant chemotherapy. Among these women, 704 were aged 35 years or younger. pCR and disease-free survival (DFS) were
Venlafaxine Lowers Endoxifen Levels, May Affect Tamoxifen Effectiveness By Caroline Helwick
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he antidepressant venlafaxine is often prescribed to dominantly CYP2D6 extensive and ultrarapid metabolizers. patients with breast cancer who are taking tamoxifen, Venlafaxine significantly decreased endoxifen concentrations. to help reduce the side effect of hot flashes. But accord- Across all genetic subgroups, levels were depressed by a mediing to research presented at the 2012 CTRC-AACR San an of about 1.6 ng/mL over time (P = .04). Limited evidence Antonio Breast Cancer Symposium, venlafaxine may reduce suggests that at least 6 ng/mL is needed for the prevention of the effectiveness of the drug. breast cancer events; in the present study, 3 women with low The findings came from a multicenter prospective phar- CYP2D6 activity had levels drop below that. macologic study that analyzed paired blood samples from Goetz acknowledged that the optimal endoxifen concen30 women taking venlafaxine for at least 4 weeks for the tration needed for benefit is still unknown, as is the effect of treatment of hot flashes. Blood was taken before starting venlafaxine on breast cancer outcomes. “The bottom line is venlafaxine and 8 to 16 weeks afterthat there is a decrease [in concenward. Genotyping was conducted for tration]. It’s small but it’s statisticalWomen with tamoxifenalleles associated with no, reduced, and ly significant. The question really ultrarapid metabolism. The aim was to is, ‘Are there subgroups of patients induced vasomotor examine whether venlafaxine altered in which this is important?’” symptoms requiring the pharmacokinetics of tamoxifen He concluded that “given prior and to determine the distribution of data linking low endoxifen conameliorative treatment CYP2D6 genotypes in this population. centrations with recurrence, venlawith venlafaxine were CYP2D6 is the rate-limiting faxine should be used with caution enzyme responsible for the metabolic in tamoxifen-treated patients.” predominantly CYP2D6 activation of tamoxifen to endoxifen. Session moderator Hiltrud extensive and ultrarapid Among women taking tamoxifen, Brauch, PhD, of the Margarete those who are extensive metabolizers Fischer-Bosch Institute of Clinimetabolizers. of CYP2D6 have higher endoxifen cal Pharmacology in Stuttgart, concentrations, have more vasomoGermany, led a 2009 study showtor symptoms, and are more likely to discontinue treat- ing that variations in CYP2D6 metabolism have an effect on ment, compared with poor metabolizers. disease-free and event-free survival in patients taking tamoxi“The data regarding CYP2D6 genotype and cancer recur- fen. “Poor metabolizers do not benefit from tamoxifen as well rence [have] been mixed,” said lead investigator Matthew as extensive metabolizers,” she said. “The long and the short Goetz, MD, of the Mayo Clinic in Rochester, Minnesota. of it is that this matters to women.” l “Venlafaxine is a weak CYP2D6 inhibitor not known to alter tamoxifen pharmacokinetics and is commonly recommended Reference Goetz MP, Suman V, Henry NL, et al. Venlafaxine inhibits the CYP2D6 medifor tamoxifen-induced hot flashes.” ated metabolic activation of tamoxifen: results of a prospective multicenter study: Women with tamoxifen-induced vasomotor symptoms (NCT00667121). Presented at: 2012 CTRC-AACR San Antonio Breast Cancer requiring ameliorative treatment with venlafaxine were pre- Symposium; December 4-8, 2012; San Antonio, TX. Abstract PD10-08.
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compared for the younger patients (aged ≤35 years) versus women aged 36 to 50 years and women aged 51 years or older. A greater percentage of younger women had triple-negative breast cancer (32% for younger women, about 25% for those aged 26-50 years, and 21% for those aged 51 years and older). Compared with older women, a smaller percentage of younger women had luminal-A–type breast cancer (27% vs 21%, respectively). pCR was significantly higher in younger women compared with older women: 23.6% versus 17.5% of women in the 36- to 50-year-old age group and 13.5% of those aged 51 years and older (P <.001); this difference in pCR was confined to triple-negative and luminal-like breast cancer (HR+/HER2–). More in-depth analysis showed that this difference was restricted to women with triple-negative breast cancer: the pCR rate was 45% for younger patients versus 31% for older patients (P <.001). For all patients, regardless of subtype of breast cancer, DFS and local recurrence-free survival were significantly worse for the very young patients (aged ≤35 years) compared with middle-aged patients (aged 36-50 years; P = .031 and P = .018, respectively). No difference in DFS according to age was observed among patients who achieved pCR. However, DFS was significantly worse among women who failed to achieve pCR. Tumor biology appeared to be important in predicting pCR and survival in younger women. Age but not pCR predicted DFS in women with luminal-A– type cancer. However, the worst DFS rate was seen among those women with luminal-A–type breast cancer who were younger than age 35 years and did not achieve pCR. The most favorable DFS was observed among younger women who did achieve pCR. Loibl said the investigators were surprised to find that younger women with luminal-type cancer (HR+ and HER2–) who achieved pCR had improved survival compared with patients with nonpathologic CR. “This is not seen in other age groups, indicating that breast cancer in the young women is chemosensitive, even when it is a luminal-type breast cancer,” she stated. l Reference
Loibl S, Jackisch C, Gade S, et al. Neoadjuvant chemotherapy in the very young 35 years of age or younger. Presented at: 2012 CTRC-AACR San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX.
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