Jane Howard

Integrated Positron Emission Tomography/Computed Tomography May Render Bone Scintigraphy Unnecessary to Investigate Suspected Metastatic Breast Cancer

PURPOSE Although the accurate detection of osseous metastases in the evaluation of patients with suspected metastatic breast cancer (MBC) has significant prognostic and therapeutic implications, the ideal diagnostic approach is uncertain. In this retrospective, single-institution study, we compare the diagnostic performance of integrated positron emission tomography/computed tomography (PET/CT) and bone scintigraphy (BSc) in women with suspected MBC. PATIENTS AND METHODS Women with suspected MBC evaluated with PET/CT and BSc (within 30 days) between January 1, 2003 and June 30, 2008, were identified through institutional databases. Electronic medical records were reviewed, and radiology reports were classified as positive/negative/equivocal for osseous metastases. A nuclear medicine radiologist (blinded to correlative and clinical end points) reviewed all equivocal PET/CT and BSc images and reclassified some reports. Final PET/CT and BSc classifications were compared. Baseline patient/tumor characteristics and bone pathology were recorded and compared to the final imaging results. RESULTS We identified 163 women who had a median age of 52 years (range, 30 to 90 years); 32% had locally advanced breast cancer, 42% had been diagnosed with breast cancer less than 12 weeks before identification. Twenty studies were originally deemed equivocal (five with PET/CT, and 15 with BSc), and 13 (65%) of these studies were reclassified after radiology review. Overall, PET/CT and BSc were highly concordant for reporting osseous metastases with 132 paired studies (81%); 32 (20%) were positive, and 100 (61%) were negative. Thirty-one occurrences (19%) were discordant. Twelve of these (39%) had pathology confirming osseous metastases: nine (of 18) were PET/CT positive and BSc negative; one (of three) was PET/CT positive and BSc equivocal; and two (of two) were PET/CT equivocal and BSc negative. CONCLUSION This study supports the use of PET/CT in detecting osseous metastases for suspected MBC. Whether PET/CT may supplant BSc in this setting is unknown.

Adjuvant trastuzumab with chemotherapy is effective in women with small, node‐negative, HER2‐positive breast cancer

Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node‐negative HER2‐positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single‐institution, sequential cohort study of women with small, node‐negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted.

Current or recent pregnancy is associated with adverse pathologic features but not impaired survival in early breast cancer

Pregnancy‐associated breast cancer (PABC) may be defined as breast cancer diagnosed during pregnancy or within 1 year of giving birth. Conflicting data exist regarding the impact of pregnancy on clinical features and prognosis of breast cancer.

Standardized uptake value by positron emission tomography/computed tomography as a prognostic variable in metastatic breast cancer†

In this retrospective, single‐institution study, the authors examine the maximum standardized uptake value (SUVmax) on positron emission tomography/computed tomography (PET/CT) images as a prognostic variable in patients with newly diagnosed metastatic breast cancer (MBC).

Patterns of toxicity in older patients with breast cancer receiving adjuvant chemotherapy.

SummaryObjective. To retrospectively determine the relationship of age to toxicity from adjuvant chemotherapy for breast cancer.Design and Methods We identified 1405 consecutive patients age 65 or older with primary invasive breast cancer who were seen at Memorial Sloan-Kettering Cancer Center from January 1998 to December 2000. Patients selected from this cohort for analysis were aged 65 or older at diagnosis; received their follow-up care at Memorial Sloan-Kettering Cancer Center; had stage I, II, or III breast cancer; and received adjuvant chemotherapy consisting of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil), an anthracycline-based regimen (AC [doxorubicin and cyclophosphamide], or AC-T [AC and paclitaxel or docetaxel]). Exclusion criteria included prior chemotherapy or previous breast cancer. Results. One hundred thirty-two patients were included in this study, with a mean age of 70 (range 65–79). Comorbidity measured by the Charlson comorbidity index was low: score 0 (83%), 1 (12%), 2 (5%); with stages: I(18%), IIA (41%), IIB (27%), IIIA (8%), IIIB (6%), T1Nx (1%). Patients receiving an anthracycline-based regimen were more likely to experience grade 3 or 4 toxicity (p=0. 01), require hospitalization (p<0.001), and/or develop febrile neutropenia (p<0.001). Treatment delays due to myelosuppression occurred more frequently in patients receiving CMF (p<0.001). The type of chemotherapy regimen (anthracycline compared to CMF) was a better predictor for toxicity than increased age or comorbidity score. Conclusions. In this cohort of older patients with breast cancer, the risk for toxicity from adjuvant chemotherapy depended more on the type of regimen (anthracycline vs. CMF) than the patient’s chronological age.

Effect of Creatinine Clearance on Patterns of Toxicity in Older Patients Receiving Adjuvant Chemotherapy for Breast Cancer

ObjectiveA number of age-related physiological changes contribute to an increased risk of toxicity of cancer chemotherapy in the elderly. One of the most important of these changes is the progressive decline in renal function with aging. We sought to determine the association between calculated creatinine clearance (CLCR) and grade 3 or 4 toxicities during adjuvant chemotherapy in women ≥65 years of age with breast cancer.Design and methodsWe identified 1405 patients ≥65 years of age who had been treated for primary invasive breast cancer at Memorial Sloan-Kettering Cancer Center between January 1998 and December 2000. Patients were included in this analysis if they had stage I–III breast cancer and had received adjuvant chemotherapy. Patients were excluded if they had a prior history of breast cancer or chemotherapy, or had no baseline creatinine value available for review.ResultsThe 126 patients who met our criteria had received either cyclophos-phamide, methotrexate and fluorouracil (CMF) [n = 65, mean age 71, range 65–78] or an anthracycline-based regimen (n = 61, mean age 69, range 65–79). The majority of patients (97%) had a normal creatinine. CLCR, as calculated by the Cockcroft-Gault and Jeliffe formulas, decreased with increasing age (increased age associated with decreased Cockcroft-Gault [p = 0.02]; increased age associated with decreased Jeliffe [p < 0.01]). In multivariate analysis, after controlling for age and co-morbidity, a CLCR <50 mL/min by the Cockcroft-Gault formula was associated with an increased risk of fever and neutropenia (odds ratio [OR] 3.60; 95% CI 1.00, 12.94; p = 0.05) and a CLCR <50 mL/min by the Jeliffe formula was associated with a trend towards an increased risk of fever and neutropenia (OR 3.30; 95% CI 0.91, 12.33; p = 0.07), grade 3 or 4 haematological toxicity (OR 2.43; 95% CI 0.90, 6.55; p = 0.08), and need for erythropoietin (OR 4.15; 95% CI 0.81, 2.99; p = 0.09). An increase in creatinine (as a continuous variable) was associated with a trend towards an increased risk of grade 3 or 4 haematological toxicity (OR 5.81; 95% CI 0.96, 35.33; p = 0.06).ConclusionsIn this cohort of older breast cancer patients, a decreased CLCR and increased creatinine was associated with an increased risk of fever and neutropenia or haematological toxicity. CLCR should be considered when determining chemotherapy dosage in the elderly.

Cisplatin, vindesine and bleomycin (CVB) combination chemotherapy of advanced non-small cell lung cancer

Fifty‐four patients with advanced squamous, large‐cell or adeno‐carcinoma of the lung were treated with a three drug regimen of high‐dose cisplatin, vindesine and a four‐day bleomycin infusion (CVB). All patients had measurable disease; none had previously received chemotherapy. Of 52 patients evaluable for response, 20 (38%) had complete or partial remissions. The median duration of remission was 8 months (range, 6 1/2‐19+ months), with eight patients continuing in remission. The median duration of survival for responding patients was 16 months versus five months for nonresponding patients (P > 0.001). Toxicity included mild to moderate myelosuppression, peripheral neuropathy, and nephrotoxicity, and was generally manageable. The addition of a four‐day bleomycin infusion did not appear to offer a significant advantage over the combination of high‐dose cisplatin and vindesine in the treatment of NSCLC. The response rate and survival duration produced by the CVB protocol were similar to those reported for the two‐drug combination of vindesine and high‐dose cisplatin.

Limited overall survival in patients with brain metastases from triple negative breast cancer.

Abstract:  Patients with breast cancer, which lacks ER, PR, and HER2; “triple negative” (TNBC), are at increased risk of brain metastases (BMs). However, the impact of modern therapy on the risk of BMs and outcomes remains largely unknown. In this retrospective, single‐institution study we assessed the incidence of BMs, the therapeutic options, and overall survival, in a recent cohort of patients with TNBC. Women diagnosed with early stage TNBC from January 1, 1998 to December 31, 2007 were identified through institutional databases. Electronic medical records were reviewed to assess patterns of recurrence, treatment, and survival. In total, 1,323 patients, median age 53 years (range 20–91), were identified. There were 298 patients (23%) who developed metastatic disease, of whom, 99 (33%) developed BMs, representing 7.5% of the entire cohort. Following BM diagnosis, treatment consisted of: radiotherapy 87 (88%) patients, resection 26 (26%) patients, and systemic chemotherapy 70 (71%) patients, with a median of 1.0 (range 0–8) chemotherapy regimens. The actuarial median survival from diagnosis of BMs is 5 months (95% CI 4–7 months). This single‐institution, retrospective study confirms that the prognosis for patients with BMs from TNBC remains poor. This group of patients urgently needs improved therapies.

Change in Cycle 1 to Cycle 2 Haematological Counts Predicts Toxicity in Older Patients with Breast Cancer Receiving Adjuvant Chemotherapy

PurposeTo determine the association between changes in complete blood counts and grade 3 or 4 toxicities from cycle 1 to cycle 2 during adjuvant chemotherapy in women ≥65 years of age with breast cancer.Design and methodsA retrospective review was performed on 1405 patients ≥65 years of age who were treated for primary invasive breast cancer at Memorial Sloan-Kettering Cancer Center between January 1998 and December 2000. From this cohort, we identified patients with stage I–II breast cancer who received adjuvant chemotherapy: cyclophosphamide, methotrexate and fluorouracil (CMF) or the anthracycline-based regimens doxorubicin and cyclophosphamide (AC) or AC followed by paclitaxel (AC-T). Patients were excluded from the analysis if they had a prior history of breast cancer or chemotherapy, or if they had no baseline blood counts available for review. Toxicities, dose modification and causality were recorded.ResultsThe 104 patients who met our criteria had received either CMF (n = 58; mean age 70.6 years, range 65–78) or an anthracycline-based regimen (n = 46; mean age 68.9 years, range 65–77). Of these patients, 50% experienced treatment delay or treatment-related grade 3 or 4 toxicity. A decrease in white blood cell count and absolute neutrophil count from cycle 1 to cycle 2 was associated with grade 3 or 4 haematological toxicity, febrile neutropenia, hospitalisation and initiation of filgrastim for secondary prophylaxis. A decrease in haemoglobin was associated with febrile neutropenia and hospitalisation. Advanced age was not associated with a significant change in complete blood counts, other than a decline in absolute neutrophil count in patients receiving CMF.ConclusionsIn this cohort of older patients who received chemotherapy for breast cancer, changes in blood counts from cycle 1 to cycle 2 were associated with increased risk of treatment-related grade 3 or 4 toxicity.

Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma

Oncotype Dx Breast Cancer Assay is a 21‐gene assay used in estrogen receptor (ER)‐positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER‐2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision‐making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions.