Carol Connor

A comparison of prognostic tumor markers obtained on image-guided breast biopsies and final surgical specimens

BACKGROUND This study was initiated to determine whether tumor markers obtained on image-guided breast biopsy specimens provide accurate prognostic information for women with invasive breast cancer. METHODS Prognostic tumor markers on preoperative image-guided biopsy and final surgical specimens were compared in 44 patients with invasive breast cancer. RESULTS Progesterone receptor (PR) discordance was 18%. In 87% of PR discordant cases, the image-guided biopsy was positive and the final specimen was negative (P = 0.03). Tumor grade was discordant in 36% of patients Discordance for estrogen receptor (ER) = 2%; MIB-1 = 18%; Her2/neu = 9%; EGFR = 10%; p53 = 9%; and bcl-2 = 0%. The discordance for these markers was random and did not reach statistical significance. CONCLUSION Image-guided core needle biopsies provide reliable information for the majority of prognostic tumor makers. A positive progesterone receptor is significantly more likely to be determined by core biopsy rather than the final surgical specimen. Tumor grade should be based upon the final surgical specimen whenever possible.

Significance of tumor spread in adenocarcinoma of the ampulla of vater

Twenty-eight patients with ampullary carcinoma were treated between 1965 and 1988: 22 underwent pancreaticoduodenectomy with 1 operative death (5 percent), 1 had local excision, 3 had bypass, and 2 were not explored. Of the 21 patients who survived pancreaticoduodenectomy, 4 had tumor confined to the ampulla, 7 had tumor extending into the duodenum, and 10 had tumor invasion beyond the duodenum. Nine of these patients had positive lymph nodes and 12 had negative lymph nodes. The patient who had local excision was disease-free at last follow-up 104 months postoperatively. Each of the three bypassed patients died of tumor progression within 15 months. The estimated 5-year survival rate for resected patients was 60 percent and was independently related to lymph node metastases (p = 0.031) and to tumor size (p = 0.039). This experience suggests that long-term survival is possible in patients with lymph node metastases or invasive tumors extending beyond the duodenal wall and that curative pancreaticoduodenectomy can be performed with a low operative mortality; therefore, aggressive surgical resection is recommended for all patients with ampullary carcinoma.

Local recurrence following breast conservation therapy in African-American women with invasive breast cancer.

BACKGROUND African-American women have a lower survival rate than white women following a diagnosis of invasive breast cancer. Limited information is available regarding the impact of race on results of breast conservation therapy (BCT). METHODS Local recurrence rates were compared in 71 African-American patients (73 breasts) and 204 white patients (208 breasts) with stage I and II breast cancer treated with BCT. RESULTS Overall 5-year actuarial recurrence rates were 13% in African-Americans and 4% in whites (P = 0.075). These rates were 9% and 4%, respectively, if patients with local skin/soft tissue recurrences were excluded (P = 0.587). Exclusion of these skin/soft tissue failures eliminated any significant difference seen in recurrence between stage II African-American and white patients (P = 0.163). African-American women had less favorable recurrences, including tumor in more than one quadrant or local skin/ soft tissue involvement (P = 0.001). CONCLUSIONS Overall actuarial recurrence rates were slightly higher, but not significantly different, in African-American and white women following BCT. A much less favorable pattern of local recurrence was seen in the African-American patients (P = 0.001), which may represent the presence of more biologically aggressive tumors in these women.

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.

Grading invasive ductal carcinoma of the breast: advantages of using automated proliferation index instead of mitotic count

Breast carcinomas are graded according to the “Nottingham modification of the Bloom–Richardson system” (SBR). The system is hindered, however, by lack of precision in assessing all three parameters including nuclear grade, mitosis, and tubular formation, leading to an element of subjectivity. Our objective was to evaluate a new grading system [the nuclear grade plus proliferation (N+P) system] for subjectivity, ease, and better representation of tumor biology. Its components are nuclear grade and automated proliferation index. Invasive ductal carcinomas, consisting of 137 SBR grade I, 247 grade II, and 266 grade III, were re-evaluated by the N+P system. The two systems were compared with each other and correlated with patients’ overall survival, tumor size, angiolymphatic invasion, lymph node status, and biomarker status including estrogen receptor, progesterone receptor, p53, epidermal growth factor receptor, BCL-2, and Her-2. Although there was an agreement between the two systems with histologic and prognostic parameters studied, there was 37% disagreement when grading individual tumors. Fifty-three percent of SBR grade II tumors were “down-graded” to N+P grade I, and 7% were “up-graded” to N+P grade III. Distinction among the different histologic grades for overall survival curves was better indicated by the N+P than the SBR system.

Effect of biliary decompression on morbidity and mortality of pancreatoduodenectomy

To evaluate the effect of levels of serum bilirubin on morbidity and mortality after pancreatoduodenectomy, a prospective study was designed to compare patients who underwent preoperative biliary decompression to those who did not. Preoperative biliary decompression decreased the mean serum bilirubin level from 15.8 to 5.8 mg/dl in one group of 10 patients (Group A). The only statistical differences between this group and the two other groups of patients (Groups B and C) who were not treated with preoperative biliary decompression was the level of serum bilirubin before pancreatoduodenectomy (5.8, 22, and 1.3 mg/dl in Groups A, B, and C, respectively). Only one death occurred in each group of patients. The numbers of nonfatal complications were comparable. These results suggest that there is no decrease in morbidity or mortality after pancreatoduodenectomy when the serum bilirubin level is decreased by preoperative biliary drainage.

Radioiodine therapy for differentiated thyroid carcinoma

Radioiodine (iodine 131) is an effective form of adjuvant therapy that is frequently underutilized. A review of our recent experience was undertaken to assess the role of this treatment modality in the routine management of thyroid carcinoma. Over a 2-year period, 29 patients received adjuvant iodine 131 therapy. Ten of these patients (35 percent) were found to have local or distant metastasis by iodine-131 scan, and 7 (24 percent) had a metastatic lesion not suspected by operative findings or chest radiography. A complete response was obtained in 70 percent of the patients with metastatic disease. This study supports more frequent use of adjuvant radioiodine therapy in the management of differentiated thyroid carcinoma.

Parathyroid hormone-like peptide and parathyroid hormone are secreted from bovine parathyroid via different pathways.

Parathyroid hormone-like peptide is a recently discovered protein which is thought to be responsible for the hypercalcemia of malignancy. Through the use of radioimmunoassay, Northern analysis and Western blot techniques this protein has been demonstrated to occur in a variety of tumor and normal cells. Its role in normal physiology is not established nor is there knowledge regarding its synthesis, secretion, and storage. We have investigated characteristics of the secretion of parathyroid hormone-like peptide in bovine parathyroid gland slices and cells to learn whether or not this protein is secreted in a manner similar to that of parathyroid hormone. We have used radioimmunoassays specific for PTH and PTH-rP to measure the secretion of each protein and have found that, unlike PTH, PTH-rP secretion was not influenced by the medium calcium concentration. Similarly, PTH-rP secretion was not influenced by other known PTH secretagogues such as c-AMP or isoproterenol. An examination of the subcellular distribution of PTH-rP revealed that 75-90% of it occurs in the soluble fraction of cell lysates. Analysis of isolated secretory granules demonstrated the presence of PTH while PTH-rP was undetectable in these organelles. We conclude that PTH-rP is not secreted from parathyroid cells via the regulated pathway utilizing PTH secretory granules.

Factors associated with success of the extreme drug resistance assay in primary breast cancer specimens

The extreme drug resistance (EDR) assay has not been widely studied in the setting of non-metastatic breast cancer. We evaluated the feasibility of performing the assay in 144 primary breast tumor specimens from two institutions by determining the rate of successful tumor culture for assays, number of drugs evaluated per assay, and time from tumor biopsy to receipt of results. We also sought to determine factors that are associated with assay success. An exploratory analysis was performed to detect possible associations between estrogen receptor (ER), progesterone receptor (PR) and HER2/NEU over-expression and extreme drug resistance demonstrated by the assay for specific chemotherapeutic agents. Of 144 tumor specimens submitted, tumor was successfully cultured for assay in 101(70%) of cases. A median of five drugs was evaluated per assay (range 2–9). Results were obtained in a median of 8 days (range 2–29). Young age, high tumor grade, PR negativity, and higher tumor submission weight were predictive for a successful assay. EDR was observed in 7–15% of tumors to doxorubicin, cyclophosphamide, 5-fluorouracil (5FU) and mitoxantrone, but EDR to paclitaxel was observed in 35%. Extreme drug resistance to 5-FU was associated with negative ER and PR status. There was a trend toward association between EDR to paclitaxel and HER2/NEU over-expression. The EDR assay may be successfully performed in the majority of tumors, and assay results are available in a timely fashion such that adjuvant treatment drug selection could be guided by results. These results may be helpful for designing possible future trials that evaluate the assays role in adjuvant chemotherapy selection.

Impact of neoadjuvant chemotherapy on axillary nodal involvement in patients with clinically node negative triple negative breast cancer.

We evaluated the impact of Neoadjuvant Chemotherapy (NAC) versus primary surgery (PS) on axillary disease burden/surgery in clinically node negative Triple Negative Breast Cancer (TNBC).