A total of 2,600 patients age 60 and older were seen in consultation by breast medical oncologists at MSKCC between October 1, 2002 and June 28, 2005. Of these, 162 patients met the criteria of the cohort as defined above. Most of those who were ineligible did not receive chemotherapy or did not pursue follow-up care at MSKCC.
The average age of patients included in this analysis was 66 (SD 4.7; range 60–76). The median age was 65. Of 162 patients, 123 (76%) were aged 60–69 and 39 (24%) were older than 69. Ninety-nine percent (n = 160) of the patients were female, and had the following breast cancer stages: 3% stage I (n = 5), 69% stage II (n = 111), and 28% stage III (n = 46). Seventy-three percent (n = 119) of tumors were positive for estrogen and/or progesterone receptors. Seventeen percent (n = 27) were HER2-neu amplified by FISH analysis.
The prevalence of comorbid medical conditions was assessed using the Charlson comorbidity index. The majority of patients had a low comorbidity score. Seventy-three percent of patients (n = 118) had a score of zero, 18% (n = 29) had a score of 1, 7% (n = 11) had a score of 2, and 2% (n = 4) had a score of 3 (). Therefore, most patients had few other medical problems that would significantly contribute to a 1-year mortality risk. Eighty-five percent (n = 138) of patients were receiving adjuvant chemotherapy, and 15% (n = 24) were receiving neoadjuvant chemotherapy.
Fig. 1 Percent of Older Breast Cancer Patients with Comorbid Medical Conditions as Assessed by Charlson Comorbidity Index* (N = 162). * The Charlson comorbidity index weights the following comorbid medical disease: myocardial infarction, congestive cardiac failure, (more ...)
shows the percent of patients who did not complete the full course of chemotherapy. Twenty-two percent (n = 36) did not complete the planned 8 cycles of treatment, 6% (n = 10) during the AC portion and 16% (n = 26) during the taxane portion. The most common reasons for treatment discontinuation included patient preference (5%), allergic reaction to chemotherapy (3%), grade 3 neutropenic fever (2%), and grade 3 fatigue (2%). The less common reasons for discontinuation observed in <1% of patients included: grade 2 thrombocytopenia and sensory neuropathy; grade 3 mucositis, pneumonitis, depression, confusion, myopathy, infection, anemia, neutropenia; grade 4 neutropenia, hyponatremia, pulmonary embolism; and/or no change in tumor size. One patient experienced a treatment-related mortality secondary to grade 5 pneumonitis that occurred after the patient’s first cycle of paclitaxel.
Percent of Older Breast Cancer Patients Who Did Not Complete a Full Course of Dose-Dense Chemotherapy (N = 162). Abbreviations: AC, doxorubicin, cyclophosphamide; T, paclitaxel
displays the percent of patients who received standard dosing and dose reductions. The standard dose of AC was defined as doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2; T was defined as paclitaxel 175 mg/m2. Twelve (7%) patients required dose reductions; 10 reductions occurred during the AC segment of treatment and 2 during the T portion. An additional 8 (5%) patients switched during the T segment of treatment from paclitaxel to docetaxel, most often for allergic reaction to the paclitaxel infusion.
Percent of Older Breast Cancer Patients Requiring Dose Reduction of Dose-Dense Chemotherapy (N = 162). Abbreviations: AC, doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2; T, paclitaxel 175 mg/m2
summarizes the common toxicities documented during treatment. Forty-one percent of patients (n = 67) experienced at least one grade 3 or 4 toxicity. Seventeen percent (n = 27) experienced at least one grade 3 or 4 hematologic toxicity, while 36% (n = 59) experienced at least one grade 3 or 4 nonhematologic toxicity. The most common hematologic toxicities were neutropenia, leukopenia, and anemia; the most common nonhematologic toxicities were infection and fatigue. Five percent (n = 8) experienced neutropenic fever.
Common toxicities in older breast cancer patients treated with dose-dense AC-T chemotherapy
Age was not statistically associated with the risk of grade 3 or 4 toxicities (41% < age 70; 44% ≥ 70; P = 0.85); however, age 70 and older was associated with a statistically significant increase in the receipt of blood transfusion (5% < age 70; 15% ≥ 70; P = 0.04) (). Patients age 70 and older were more likely to have comorbid medical conditions (Charlson score 1, 2, or 3); however, this was not statistically significant (24% < age 70; 36% ≥ age 70; P = 0.21). A multivariate analysis was performed to determine the association of significant toxicity with age, presence of comorbidity, and baseline hemoglobin (). Even though age ≥ 70 was not significantly associated with risk of grade 3 or 4 toxicities in bivariate analyses, we still included it as a covariate in multivariate analysis in order to assess whether age became an important factor after adjusting for the presence of comorbidities. Age was not significantly associated with the probability of having any grade 3 or 4 toxicity, grade 3 or 4 hematologic toxicity, or grade 3 or 4 nonhematologic toxicity. However, a statistically significant association was found between comorbidity score and any grade 3 or 4 toxicity (P = 0.04) and grade 3 or 4 nonhematologic toxicity (P < 0.01). In addition, a statistically significant association was found between baseline hemoglobin score and any grade 3 or 4 toxicity (P = 0.04), grade 3 or 4 hematologic toxicity (P = 0.02), and grade 3 or 4 nonhematologic toxicity (P = 0.05). The odds of having a grade 3 or 4 hematologic toxicity is 1.57 times higher with every unit decrease in baseline hemoglobin. The odds of having a grade 3 or 4 nonhematologic toxicity among patients with a Charlson comorbidity index score of 1 or more is 2.97 times higher than the odds among patients with a Charlson comorbidity index score of 0.
Association of age category with outcomes in older patients with breast cancer given dose-dense chemotherapy
Predictors of toxicity with dose-dense chemotherapy in older breast cancer patients