Daniel Hendler

Adjuvant Docetaxel and Cyclophosphamide (DC) with Prophylactic Granulocyte Colony-Stimulating Factor (G-CSF) on Days 8 &12 in Breast Cancer Patients: A Retrospective Analysis

Purpose Four cycles of docetaxel/cyclophosphamide (DC) resulted in superior survival than doxorubicin/cyclophosphamide in the treatment of early breast cancer. The original study reported a 5% incidence of febrile neutropenia (FN) recommending prophylactic antibiotics with no granulocyte colony-stimulating factor (G-CSF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events. We explored the use of growth factor (GF) support on days 8 and 12 of the cycle with the original DC protocol. Methods Our study included all consecutive patients with stages I–II breast cancer who were treated with the DC protocol at the Institute of Oncology, Davidoff Center (Rabin Medical Center, Petah Tikva, Israel) from April, 2007 to March, 2012. Patient, tumor characteristics, and toxicity were reported. Results: In total, 123 patients received the DC regimen. Median age was 60 years, (range, 25–81 years). Thirty-three patients (26.8%) were aged 65 years and older. Most of the women (87%) adhered to the planned G-CSF protocol (days 8 &12). 96% of the patients completed the 4 planned cycles of chemotherapy. Six patients (5%) had dose reductions, 6 (5%) had treatment delays due to non-medical reasons. Thirteen patients (10.6%) experienced at least one event of FN (3 patients had 2 events), all requiring hospitalization. Eight patients (6.5%) required additional support with G-CSF after the first chemotherapy cycle, 7 because of FN and one due to neutropenia and diarrhea. In Conclusion Primary prophylactic G-CSF support on days 8 and 12 of the cycle provides a tolerable option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support.

Uncommon Reason for High Fluorodeoxyglucose Positron Emission Tomography Uptake

A 32-year-old woman presented with a local recurrence of breast cancer. She had first been diagnosed in 2006 with clinical stage II (T4.5 cm N0 M0), triple-negative breast cancer of the left breast; she received neoadjuvant chemotherapy and breast-conserving surgery followed by adjuvant chemotherapy and breast irradiation. She remained disease-free until May 2009, when a 0.9-mm lump appeared in her left breast. A trucut biopsy showed infiltrating ductal carcinoma. A computed tomography/positron emission tomography (PET) scan showed diffuse high fluorodeoxyglucose (FDG) uptake in her right breast with no pathologic findings or uptake elsewhere (Fig 1). The PET scan is one of the most useful tools for metastatic evaluation. In an extensive review of the FDG-PET literature, comprising 419 articles from 1993 to 2000, the overall sensitivity and specificity was estimated to be 84% and 86%, respectively, and results from a PET scan changed the management of one third of the patients in the literature. Tumor cells have higher metabolic rates than normal cells; therefore, they take up greater amounts of glucose and FDG than surrounding tissues do. However, it is not only tumor cells that may have an increased FDG uptake. Lesions with high concentrations of inflammatory cells may also show increased FDG uptake, which can be mistaken for malignancy in patients with proven or suspected cancer. Incidental increased FDG uptake in the thyroid can be seen in 2% of PET scans, including scans of Graves’ disease. Increased FDG uptake has also been reported in the normal uterus during menstruation; in healing bone, joints, and sites of infection; in granulomatous diseases like sarcoidosis; in chronic inflammatory diseases like tuberculosis; and in other infrequent conditions like LhermitteDuclos disease. Some other rare reasons for high FDG uptake include atherosclerotic plaque formation, adenomatous polyps of the colon, diffuse bone marrow uptake after erythropoietin or granulocyte colony-stimulating factor administration, and thalassemia. Finally, high FDG uptake has also been reported in breast-feeding women. In this patient, there was no FDG uptake in her left breast recurrence of a tumor the size of less than 1 cm under the scan resolution. Unexpectedly, there was an extensive high FDG uptake in her contralateral breast, which was otherwise clinically normal. The patient was breast-feeding her three-month-old newborn, which provides an uncommon reason for high FDG uptake that is not widely recognized as a cause for a false-positive PET scan in clinical practice. Radiation therapy may lead to a substantially reduced milk supply, even to the point of no milk at all. After having had her left breast irradiated three years before when the disease was first diagnosed, the patient’s milk production occurred in her contralateral breast only—the one showing high FDG uptake. Delay of PET scanning until after completion of breast-feeding should be considered to avoid a work-up of a false-positive result. On the other hand, if PET scanning must be performed, then breastfeeding should be interrupted both before the exam and afterward until the radioactivity has left the breast.

The Association between Angiotensin Receptor Blocker Usage and Breast Cancer Characteristics

Purpose: To evaluate the association between angiotensin receptor blocker (ARB) usage and breast cancer characteristics and outcomes. Methods: All patients who were treated in our institute for estrogen receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer between April 2005 and March 2012 and whose tumors were sent for Oncotype-DX analysis were included. Medical records were retrospectively reviewed. Data regarding ARB usage were retrieved. Usage of several prespecified medications for hypertension was also evaluated. Each medication group was compared with the rest of the cohort. Results: A total of 671 patients were included. Forty-six (7%) patients were treated with ARB. ARB usage was associated with macroscopic nodal involvement (p < 0.001) and a more advanced stage at diagnosis (p < 0.001). These findings remained significant in the multivariate analysis. Patients treated with ARB also had a higher incidence of invasive lobular carcinoma subtype (p = 0.009), a worse 5-year breast cancer-specific survival (94.7 vs. 98.8%, p = 0.024) and a worse 5-year overall survival (94.6 vs. 98.8%, p = 0.015), but these differences were not demonstrated in the multivariate analysis. Conclusions: Patients treated with ARB presented with a more advanced breast cancer disease and some distinct histological features. Further research is required to elucidate the effect of ARB treatment on breast cancer.

The Association between Treatment for Metabolic Disorders and Breast Cancer Characteristics

Purpose. To evaluate the associations between metformin, insulin, statins, and levothyroxine and breast cancer characteristics and outcome. Methods. Retrospective chart review of patients treated in our institute for early estrogen receptor (ER) positive, human epidermal growth factor receptor 2 negative breast cancer, whose tumors were sent to Oncotype DX (ODX) analysis. Patients were grouped according to medications usage during the time of breast cancer diagnosis. Each group was compared to the rest of the study population. Results. The study cohort included 671 patients. Sixty (9.1%) patients were treated with metformin, 9 (1.4%) with insulin, 208 (31.7%) with statins, and 62 (9.4%) with levothyroxine. Patients treated with metformin had more intense ER stain (p = 0.032) and a lower ODX recurrence score (RS) (p = 0.035). Diagnosis of diabetes mellitus was also associated with lower ODX RS (p = 0.014). Insulin usage was associated with a higher rate of angiolymphatic invasion (p = 0.041), but lower Ki67% (p = 0.017). Levothyroxine usage was associated with different histological subtype distribution (p = 0.02). Extended levothyroxine usage was associated with lower ODX RS (p = 0.005). Statin usage had no impact on tumor characteristics. Outcome was comparable in the studied subgroups. Conclusions. Common medications for metabolic disorders might be associated with breast cancer characteristics.

Abstract P5-08-25: The association between smoking and breast cancer characteristics and outcome

Background: Smoking is associated with an increased incidence of hormone receptor positive breast cancer. Data regarding worse breast cancer outcome in smokers are accumulating. Current literature regarding the impact of smoking on breast cancer characteristics is limited. The aim of this study was to evaluate the impact of smoking on the characteristics and outcome of estrogen receptor positive, human epidermal growth factor receptor 2 (HER2) negative early breast cancer. Methods: This was a retrospective single center study. All patients diagnosed from 4/2005 through 3/2012 and treated in our institute for early, estrogen receptor positive, HER2 negative breast cancer, whose tumors were sent for Oncotype DX analysis were included. Medical records were reviewed for demographics, clinico-pathological parameters, treatment and outcome. Patients were grouped and compared according to smoking history (present or past smokers vs. never smokers) and status (current vs. former and never smokers). Heavy smokers (pack years ≥30) were analyzed separately. Results: A total of 671 patients were included. 28.7% had a history of smoking, 17% were current smokers and 11.5% were heavy smokers. Smoking had no impact on tumor size, nodal involvement and Oncotype DX recurrence score. Angiolymphatic and perineural invasion rates were higher in current smokers than in the rest of the cohort (11% vs. 5.1%, p=0.023, 9% vs. 3.45%, p=0.013, respectively). Smoking had no other impact regarding histological characteristics. Five-year disease free survival and overall survival rates were 95.7% and 98.5%, respectively. Smoking had no impact on outcome. Conclusions: In patients with estrogen receptor positive, HER2 negative, early breast cancer, smoking had no clinically significant influence on tumor characteristics and outcome. As the study was limited to a specific subgroup of the breast cancer population in this heterogeneous disease and since smoking is a modifiable risk factor for the disease, further research is required to clarify the possible impact of smoking on breast cancer. Citation Format: Goldvaser H, Gal O, Rizel S, Hendler D, Neiman V, Shochat T, Sulkes A, Brenner B, Yerushalmi R. The association between smoking and breast cancer characteristics and outcome [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-25.

Adjuvant docetaxel and cyclophosphamide (DC) with prophylactic growth colony stimulating factor (GCSF) on days 8 and 12 in breast cancer patients: A retrospective analysis.

202 Background: Four cycles of docetaxel/cyclophosohamide (DC) produced superior survival compared with doxorubicin/cyclophosphamide in the treatment of early breast cancer. The study reported 5% of febrile neutropenia (FN) events using prophylactic antibiotics with no growth factor (GF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events (up to 46%), prompting the addition of GCSF by most centers. We explored the use of GF support on days 8 and 12 to the original DC protocol. This report summarizes treatment related morbidity of the DC protocol with GF support given on days 8 and12. METHODS All consecutive patients with stages I-II breast cancer who were treated with the DC protocol in our institute from April 2007 to March 2012 were included. Patient characteristics and toxicity were reported. RESULTS 131 patients were identified. Median age- 60y (25-81), 65y and older- 25%; 5 patients did not complete the 4 planned cycles (12/524 cycles were missed). Fifteen patients (11.5%) experienced at least one event of FN (4 patients had 2 events), all requiring hospitalization. FN events occurred in 19 out of 512 cycles (3%). Median age of the patients who required hospitalization due to FN was 60y (42-73). Results were comparable in the older group (≥65): 15% developed FN with 6 NF events out of 130 cycles (4.6%), p>0.05. There were additional 14 hospitalizations events due to other causes (diarrhea n=2, chest pain=2, cellulitis n=2, COPD n=1, tonsillitis n=1, fever n=2, bone pain n=1, observation after treatment n=1 and hearing problem n=1, unknown n=1). Six patients had grade 2-3 diarrhea. 2/6 required hospitalization. There was no treatment related mortality. CONCLUSIONS Primary prophylactic growth factor support on days 8 and 12 provides a safe and economic option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support.

Tailoring neoadjuvant chemotherapy for locally advanced breast cancer: a historical prospective study.

Background: Despite the growing number of clinical trials assessing preoperative systemic chemotherapy (PST) for locally advanced breast cancer, the optimal regimen has still to be defined. Purpose: This was to evaluate the toxicity, operability rate, pathological response rate and disease-free and overall survival associated with a PST regimen consisting of the sequential administration of single agents according to the individual tumor response. Methods: Medical files were reviewed of 102 consecutive patients with breast cancer treated in 2000–2007 with a neoadjuvant sequential regimen of doxorubicin followed by taxane. The number of cycles and the addition of taxane were based on tumor response. Results: Seventy percent of the patients had inoperable disease at diagnosis and 29% were given preoperative therapy for breast conservation. All patients underwent surgery, 65% achieved breast conservation. An overall pathological complete response (breast and nodes) was achieved in 14% of the patients, and a complete nodal pathologic response in 34%. At a median follow-up of 54 months, the overall survival rate was 82% and the disease-free survival rate was 70%. There was no treatment-related mortality. Febrile neutropenia occurred in 19% of the patients. Conclusions: A neoadjuvant regimen of doxorubicin with or without a sequential taxane, in which the number of cycles and the sequential administration of taxane are determined according to clinical response, appears to be safe and effective for patients with locally advanced breast cancer and yields a high rate of breast conservation. Tailored PST can spare patients receiving unnecessary chemotherapy.