[show abstract][hide abstract] ABSTRACT: To compare interobserver variations in delineating the whole breast for treatment planning using two contouring methods.
Autosegmented contours were generated by a deformable image registration-based breast segmentation method (DEF-SEG) by mapping the whole breast clinical target volume (CTVwb) from a template case to a new patient case. Eight breast radiation oncologists modified the autosegmented contours as necessary to achieve a clinically appropriate CTVwb and then recontoured the same case from scratch for comparison. The times to complete each approach, as well as the interobserver variations, were analyzed. The template case was also mapped to 10 breast cancer patients with a body mass index of 19.1-35.9 kg/m(2). The three-dimensional surface-to-surface distances and volume overlapping analyses were computed to quantify contour variations.
The median time to edit the DEF-SEG-generated CTVwb was 12.9 min (range, 3.4-35.9) compared with 18.6 min (range, 8.9-45.2) to contour the CTVwb from scratch (30% faster, p = 0.028). The mean surface-to-surface distance was noticeably reduced from 1.6 mm among the contours generated from scratch to 1.0 mm using the DEF-SEG method (p = 0.047). The deformed contours in 10 patients achieved 94% volume overlap before correction and required editing of 5% (range, 1-10%) of the contoured volume.
Significant interobserver variations suggested a lack of consensus regarding the CTVwb, even among breast cancer specialists. Using the DEF-SEG method produced more consistent results and required less time. The DEF-SEG method can be successfully applied to patients with different body mass indexes.
International journal of radiation oncology, biology, physics 10/2008; 73(5):1493-500. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cyclooxygenase-2 (COX2) plays a role in breast cancer progression at various stages starting from pre-malignant phenotype to clinical metastasis. Breast cancer metastasizes commonly to the bone and preclinical studies suggest an involvement of COX2 in this process. Detection of disseminated tumor cells in the bone marrow of patients at the time of surgery correlates with the subsequent development of clinical bone metastasis. Therefore, to investigate whether COX2 is important for breast cancer metastasis in humans, we analyzed COX2 protein expression by immunostaining of primary tumors from 112 operable stages I, II, or III patients and determined its correlation with bone marrow micrometastasis (BMM).
We detected COX2 protein in primary tumors by immunostaining with a monoclonal antibody, and tumor cells present in the bone marrow by immunostaining for epithelial cytokeratins and by morphological criteria.
COX2 expression in primary breast cancer correlated with BMM in a highly statistically significant manner (P = 0.006). Our statistical analyses of correlations of the COX2 positivity in primary tumor with other clinically relevant indicators revealed that COX2 positivity correlates with high nuclear grade (P = 0.0004). Furthermore, we were able to detect COX2 protein in BMM by immunostaining.
These studies indicate that COX2 produced in primary breast cancer cells may be vital to the initial development of BMM that may subsequently lead to osteolytic bone metastases in patients with breast cancer, and that COX2 inhibitors may be useful in halting this process.
Breast Cancer Research and Treatment 08/2008; 117(1):61-8. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent studies demonstrate improved progression-free survival (PFS) and improved overall survival (OS) with extirpation of the primary tumor in breast cancer patients who present with metastatic disease at initial diagnosis. The subset of patients who would most benefit from surgery remains unclear. This study evaluates the pathological attributes and optimum timing for surgery in patients who present with stage IV breast cancer and an intact primary.
Retrospective, single-institution review of all breast cancer patients between 1997 and 2002 presenting with an intact tumor and synchronous metastatic disease. Information collected included: demographics, tumor characteristics, metastatic sites, type/timing of surgery, and radiation/systemic therapy received. Patients initiated treatment within 3 months of their diagnosis. Patients were divided into three groups based on time interval from diagnosis date to surgery date. Disease progression and vital status at last follow-up were evaluated. Analysis of metastatic PFS (defined by progression of systemic disease) benefit in relation to surgical timing was performed.
Multivariate analysis revealed patients having only one site of metastasis, negative margins, and Caucasian race had improved PFS. Further analysis revealed non-Caucasian patients more often underwent surgical intervention for palliation versus surgery for curative intent, possibly explaining their worse outcome. Patients who underwent surgery in the 3-8.9 month or later period had improved metastatic PFS.
Surgical extirpation of the primary tumor in patients with synchronous stage IV disease is associated with improved metastatic PFS when performed more than 3 months after diagnosis. Resection should be planned with the intent of obtaining negative margins.
Annals of Surgical Oncology 07/2008; 15(6):1696-702. · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: We determined the incidence of positive sentinel lymph nodes (SLNs) in patients with ductal carcinoma in situ (DCIS) or microinvasive breast cancer (MIC) and the predictive factors of SLN metastasis in these patients.
Of 4,503 patients who underwent SLN dissection between March 1994 and March 2006 at our institution, we identified those with a preoperative diagnosis or final diagnosis of DCIS or MIC. Clinicopathologic factors were examined by logistic regression analysis.
Of the 624 patients with a preoperative diagnosis of DCIS or MIC, 40 had positive SLNs (6.4%). Of the 475 patients with a final diagnosis of DCIS or MIC, 9 had positive SLNs (1.9%). Clinical DCIS size >5 cm was the only independent predictor of positive SLN for patients with a preoperative diagnosis and patients with a final diagnosis of DCIS or MIC. Core biopsy as the method of preoperative diagnosis and DCIS size >5 cm were independent predictors for a final diagnosis of invasive carcinoma in the 149 patients who had a preoperative diagnosis of DCIS or MIC.
SLN dissection for patients with a diagnosis of DCIS should be limited to patients who are planned for mastectomy or who have DCIS size >5 cm. Patients who have a core-needle biopsy diagnosis of DCIS have a higher risk of invasive breast cancer on final pathologic assessment of the primary tumor. This information can be used in preoperative counseling of patients with DCIS regarding the timing of SLN biopsy.
American journal of surgery 07/2008; 196(1):81-7. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the anatomic distribution of gross supraclavicular nodes within the supraclavicular fossa using 2-deoxy-2-[F-18] fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, and to evaluate likely coverage of specific regions of the supraclavicular fossa using standard radiation fields.
We identified 33 patients with advanced or metastatic breast cancer who had a PET/CT scan demonstrating hypermetabolic supraclavicular lymph nodes in 2005. The locations of the involved lymph nodes were mapped onto a single CT set of images of the supraclavicular fossa. These lymph nodes were also mapped onto the treatment-planning CT dataset of 4 patients treated in our institution (2 patients with biopsy-proven supraclavicular nodes and 2 patients with clinically negative supraclavicular nodes).
We were able to determine the distribution of 52 supraclavicular lymph nodes in 32 patients. Of 32 patients, 28 (87%) had a history of metastatic disease, and 2 patients had isolated nodal recurrences. Five patients had supraclavicular nodes posterior to the vertebral body transverse process, and several lymph nodes were in close proximity to the medial field border, raising the possibility of geographic miss in these areas.
In patients with locally advanced disease, increased coverage of the supraclavicular fossa medially and posteriorly may be warranted.
International Journal of Radiation OncologyBiologyPhysics 07/2008; 71(2):435-40. · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Screening mammography guidelines for patients age 80 years and older are variable. We determined the effect of mammography use on stage at breast cancer diagnosis and survival among women of this age range.
We used the linked Surveillance, Epidemiology, and End Results-Medicare database to evaluate 12,358 women >or= 80 years of age diagnosed with breast cancer between 1996 and 2002. Patients were grouped according to number of mammograms during the 60 months before diagnosis: nonusers (0 mammograms), irregular users (one to two mammograms), and regular users (three or more mammograms). Effects of mammography on disease stage (I to IIa v IIb to IV) and survival were determined by logistic regression and Cox proportional hazards analyses.
Percentages of women with nonuse, irregular use, and regular use of mammography during the 5 years preceding diagnosis were 49%, 29%, and 22%, respectively. On multivariate analysis, patients were 0.37 times less likely to present with late-stage cancer for each mammogram obtained (odds ratio, 0.63; 95% CI, 0.63 to 0.67). Breast cancer-specific 5-year survival among nonusers was 82%, that among irregular users was 88%, and that among regular users was 94%. However, survival from causes other than breast cancer was also associated with mammography use, suggesting a bias for healthier patients to undergo mammography.
Regular mammography among women >or= 80 years of age was associated with earlier disease stage, although improved survival remains difficult to demonstrate. Health care providers should consider discussing the potential benefits of screening mammography with their older patients, particularly for those without significant comorbidity.
Journal of Clinical Oncology 05/2008; 26(15):2482-8. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Circulating tumor cells (CTCs) correlate with worse prognosis in patients with metastatic breast cancer, but there are little data on CTCs in operable patients. We hypothesized that primary tumor characteristics would predict the likelihood of identifying CTCs in patients with operable breast cancer.
Clinical and pathological data from 92 patients with operable breast cancer were collected. The CellSearch system was used to detect CTCs in 30 ml of peripheral blood. CTCs were defined as nucleated cells lacking CD45 but expressing cytokeratins 8, 18, or 19. Univariate analysis was performed to determine if the presence of any primary tumor characteristic was predictive of CTCs. As a secondary objective we evaluated if nodal or bone marrow status was predictive of CTCs.
Thirty-eight percent of patients (35/92) had evidence of CTCs, with a median number of 1.0 CTC per CTC positive patient (range 1-22). HER2 status was the sole primary tumor characteristic that reliably predicted the presence of CTCs (P = 0.01, risk ratio = 3.66). No significant association was found between the presence of CTCs and tumor size (T), estrogen receptor (ER) status, progesterone receptor (PR) status, grade, histologic type, degree of nodal involvement (N), lymphovascular invasion (LVI) or Ki-67 proliferation. Bone marrow micrometastases were found in 17/64 (26.6%) of the patients but did not correlate with the presence of CTCs.
HER2 status was the only primary tumor characteristic that correlated with the presence of CTCs. Long-term follow-up will be required to determine the significance of CTCs in operable breast cancer.
Breast Cancer Research and Treatment 04/2008; 113(3):501-7. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients who have invasive breast cancer identified after prophylactic mastectomy (PM) require axillary lymph node dissection (ALND) for lymph node staging (ie, directed ALND). Because the majority of these patients will be lymph node negative, sentinel lymphadenectomy (SLND) has been advocated at the time of PM to avoid the sequelae of unnecessary ALND. The objective of this study was to compare the efficacy of 2 surgical strategies, routine SLND versus directed ALND, in PM patients.
A decision-analytic model was created to compare the 2 surgical strategies. Model estimates were derived from a systematic literature review. The endpoints that were examined to compare the 2 strategies were the number of SLNDs performed per breast cancer detected, the number of SLNDs attempted to avoid 1 ALND in a lymph node-negative patient with occult invasive cancer, and the number of axillary complications associated with each strategy.
The prevalence of invasive cancer in patients undergoing PM was estimated at 1.9%. At this rate, 37 SLNDs were performed per 1 breast cancer detected, and 73 SLNDs were required to avoid 1 ALND in a lymph node-negative PM patient. In 1 model scenario, the probability of complications per breast cancer detected was 9-fold greater with the SLND strategy than with the directed ALND strategy (2.7 vs 0.3). The complication rates for the 2 strategies become equivalent in the model scenario when the prevalence of occult invasive cancer was projected to 28%.
Routine SLND for patients undergoing PM is not warranted given the large number of procedures required to benefit 1 patient and the potential complications associated with performing SLND in all patients.
Cancer 01/2008; 110(11):2542-50. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The unique growth pattern of invasive lobular carcinoma (ILC) poses a challenge for preoperative assessment of disease extent within the breast. Whether it similarly limits lymph node staging by ultrasound (US) and fine-needle aspiration (FNA) biopsy was the subject of the current study.
A total of 217 patients with ILC who underwent axillary US were reviewed. FNA biopsy was performed when US findings were suspicious or indeterminate. Findings were compared to literature reports of US in invasive ductal carcinoma (IDC) patients.
Axillary US was negative in 137 patients (63%) and suspicious or indeterminate in 80 patients (37%). FNA biopsy was positive in 62% (47/76 patients). Preoperative US and FNA biopsy identified 43 of 111 (39%) node-positive patients. Sensitivity of US with FNA biopsy correlated with primary tumor and nodal metastasis size. Similar results were seen in IDC populations.
US with FNA biopsy appears to be similarly useful in axillary staging of ILC and IDC patients.
American journal of surgery 11/2007; 194(4):450-5. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma.
In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS).
No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology.
BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.
American journal of surgery 11/2007; 194(4):527-31. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: The role of cyclin E as a predictive marker of response to chemotherapy remains unknown. We have previously shown that deregulation of cyclin E in an ovarian tumor cell line model enhances cyclin E-associated kinase activity and sensitizes tumor cells to cisplatinum. We hypothesized that cyclin E deregulation would predict for responsiveness to platinum-based regimens in ovarian cancer patients.
Patients who met the following criteria were retrospectively identified from the institutional tumor bank records: (a) high-grade ovarian epithelial malignancy, (b) stage III/stage IV disease, (c) optimally debulked, (d) completed platinum-based therapy. Tumor samples were analyzed for cyclin E, p21, and p27 by Western blot analysis and assessed for cyclin E-associated kinase activity.
Seventy-five patients, who met the study criteria, were identified. Cyclin E protein levels did not correlate with cyclin E-cdk2 kinase activity (Spearman's rho, 0.07; P = 0.58). Cyclin E-associated kinase activity was the only significant predictive marker for response to platinum-based therapy, with higher response rates seen in patients with higher levels of activity (P = 0.045). Cyclin E protein levels did not predict for platinum sensitivity (P = 0.20). In contrast, cyclin E protein levels, but not cyclin E-associated kinase activity, was a significant predictor for freedom from recurrence (P = 0.01 and P = 0.25, respectively).
Cyclin E overexpression and cyclin E-associated kinase activity have distinct roles in predicting for response to chemotherapy and outcome in ovarian cancer patients. These results suggest a compartmentalization of cyclin E functions in the oncogenic process.
Clinical Cancer Research 09/2007; 13(16):4800-6. · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the locoregional efficacy of multimodality treatment for breast cancer patients who present with ipsilateral supraclavicular (SCV) disease without systemic metastases.
We retrospectively reviewed the data from 71 patients with ipsilateral SCV involvement at presentation. SCV involvement in 16 patients (23%) was diagnosed by ultrasound examination only, without palpable disease. All patients were treated with curative intent using neoadjuvant chemotherapy, mastectomy or breast-conserving surgery (BCT), and radiotherapy.
The 5-year SCV control, locoregional control (LRC), disease-free survival, and overall survival rate was 90%, 77%, 30%, and 47%, respectively. Patients with persistent SCV disease after neoadjuvant chemotherapy by physical examination had a lower rate of LRC (64% vs. 86%, p = 0.026), as did those with persistent SCV disease by ultrasound examination (66% vs. 96%, p = 0.007). Of those with a complete response of SCV disease by physical examination after neoadjuvant chemotherapy, those with persistently abnormal ultrasound findings had significantly worse disease-free survival (0% vs. 55%, p = 0.03). BCT was not associated with lower rates of LRC (82% for BCT vs. 76% for mastectomy, p = 0.80).
Radiotherapy achieved excellent LRC after surgery for patients with ipsilateral SCV metastases who achieved a complete response of the SCV disease after neoadjuvant chemotherapy. For patients who achieved a complete response of the SCV disease by physical examination, ultrasonography of the SCV fossa may help assess the risk of disease recurrence. SCV involvement should not be considered a contraindication for BCT.
International Journal of Radiation OncologyBiologyPhysics 03/2007; 67(2):490-6. · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC.
A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups.
The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group (P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC.
BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.
The American Journal of Surgery 11/2006; 192(4):552-5. · 2.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Male breast cancer accounts for < 1% of breast cancers. Sentinel lymph node (SLN) operation is commonly used in the evaluation of female breast cancer patients. The purpose of this study was to determine whether SLN operation is as feasible and accurate in male patients compared with female patients.
Between 1999 and 2005, 30 men and 2,784 women underwent SLN operation. Clinical and pathologic data were reviewed and statistical analysis performed.
Men presented at an older age (p = 0.005) and with larger tumors than women (p = 0.04). The SLN was identified in 100% of men and in 98.3% of women (p = NS). The mean number of SLNs harvested was 3.5 in men and 3.0 in women (p = NS). The incidence of positive SLNs was higher in men (37.0% versus 22.3%), although this did not reach statistical significance (p = 0.1). In patients with a positive SLN there were additional non-SLNs positive in 62.5% of men, compared with 20.7% in women (p = 0.01). The median size of the largest lymph node metastasis was 10 mm in men and 3 mm in women (p = 0.03).
SLN operation in clinically node-negative men is feasible and accurate. Male breast cancer patients present at an older age and with larger tumors than female breast cancer patients. Male patients have higher nodal tumor burden reflected in a larger size of nodal metastasis and increased risk of harboring additional disease in axillary lymph nodes when the SLN is positive. Intraoperative SLN evaluation should be considered in the surgical management of male breast cancer.
Journal of the American College of Surgeons 11/2006; 203(4):475-80. · 4.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with invasive cancer identified at the time of prophylactic mastectomy (PM) will require axillary lymph node dissection for staging; therefore, many surgeons advocate sentinel lymph node (SLN) surgery at the time of PM. The current study investigates the invasive cancer rate in PM and evaluates factors associated with invasive cancer to guide SLN surgery use.
Patients undergoing PM at the M. D. Anderson Cancer Center between January 2000 and July 2005 were identified from a prospective database. Clinical, radiographic, and pathologic data were collected.
A total of 409 patients (436 PM cases) were identified; 382 underwent contralateral PM (CPM) and 27 underwent bilateral PM (BPM). Cancer was identified in 22 of 436 PM cases (5%). Of these, 14 patients (64%) had ductal carcinoma in situ (DCIS). Only 8 patients (1.8%) had invasive cancer, with a mean tumor size of 5 mm (range, 2-9 mm). There was no difference in the occult cancer rate between CPM and BPM. No cases of invasive cancer were identified in the 23 patients with BRCA mutations. Significantly increased risk of invasive cancer in the PM breast was seen in postmenopausal patients (3.7%; P = .007), patients age >60 years (7.5%; P = .008), and patients with history of invasive lobular carcinoma (9.7%; P = .0002) or lobular carcinoma in situ (LCIS) (7.7%; P = .008).
The frequency of cancer in PM is very low and the majority represents DCIS. Therefore, routine use of SLN surgery in all patients undergoing PM is not warranted. However, patients at higher risk for whom SLN surgery should be considered include older women and patients with a history of lobular cancer or LCIS.
Cancer 11/2006; 107(7):1440-7. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The risk of developing breast cancer rises with increasing age. The very elderly population (80 years of age and greater) is often excluded from both clinical trials and retrospective analyses. We performed a retrospective review of the very elderly population treated at our institution in order to assess treatment patterns and the safety of therapy in an older population.
In this institutional experience at a comprehensive cancer center, we retrospectively reviewed the charts of patients 80 years and older diagnosed with a new breast cancer between September 1, 1989, and September 1, 2004.
Two hundred thirteen patients were identified for this study. Median age was 83 (range 80-97). Median survival was 7.28 years, with a median follow up of 4 years for patients still alive at the end of the study period. Ninety-eight percent of patients (208/213) received 1 or more components of recommended multimodality treatment. Five patients refused all treatment. Overall, complications affected 12% of patients who received treatment (26/208). There were 2 deaths, 1 after surgery and 1 related to chemotherapy. The majority, 69% (18/26), of the documented complications were classified as minor. Surgery resulted in complications in 6% (11/188) of patients. Five percent (5/112) of patients who received radiation suffered adverse effects. Chemotherapy-related complications affected 30% (6/18) of treated patients. Hormonal agents resulted in complications in 3% (3/112) of patients. No correlation between the American Society of Anesthesiologists score and incidence of complication was observed (P = .58).
Very elderly patients can be safely treated with surgery and radiation in accordance with accepted recommendations for their stage of breast cancer. Treatment with surgery and/or radiation should be considered despite age and moderate comorbidity in order to affect locoregional control. Chemotherapy results in a significant incidence of complications and should be cautiously implemented in this age group. A prospective trial is necessary to assess the necessity of aggressive multimodality therapy in this very elderly population.
The American Journal of Surgery 11/2006; 192(4):541-4. · 2.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the effect of preoperative chemotherapy on the volume of tissue excised and the number of breast operations in patients undergoing breast-conserving therapy (BCT).
Preoperative chemotherapy is increasingly being used for breast cancer and increases rates of BCT. Its impact on the extent of surgery and the number of surgical procedures in BCT has never been fully defined. The extent of surgery in BCT directly affects cosmesis.
We reviewed the records of 509 consecutive patients with T1-T3, N0-N2 breast cancer who were treated in prospective randomized clinical trials of chemotherapy between 1998 and 2005. We analyzed the final surgical procedure (BCT or mastectomy), the number of operations, and, in patients who underwent BCT, re-excision rates, and the total volume of breast tissue excised [4Pi/3(width/2 x length/2 x height/2)].
A total of 241 patients underwent BCT, and 268 patients underwent mastectomy. Among BCT patients who had initial tumor size >2.0 cm, patients who received preoperative chemotherapy had significantly smaller volumes of breast tissue excised compared with patients who received postoperative chemotherapy (113 cm vs. 213 cm, P = 0.004). The re-excision rate and total number of breast operations did not significantly differ between the groups. Among BCT patients who had initial tumor size < or = 2 cm, preoperative chemotherapy had no impact on volume of breast tissue excised, re-excision rate, or number of breast operations (P > 0.05).
Among patients treated with BCT for larger breast tumors, patients treated with preoperative chemotherapy have less extensive resection, with no change in rates of re-excision.
Annals of Surgery 10/2006; 244(3):464-70. · 6.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: The anti-HER2 antibody trastuzumab (Herceptin) has been used to treat patients with breast cancers that overexpress HER2. We have demonstrated that p27(Kip1) upregulation is one of the key events that cause G(1) arrest upon trastuzumab treatment. Here, we have examined the effect of trastuzumab on expression of CDK2, Rb, E2F, NPAT and histone H4 in breast cancer cells that overexpress HER2. Trastuzumab treatment dramatically inhibited the kinase activity and expression of CDK2, whereas the kinase activity and expression of CDK4 were not affected. Unlike the p27(Kip1) upregulation that occurs primarily through post-translational mechanisms, CDK2 was downregulated primarily at a transcriptional level as shown by Northern blotting and real-time RT-PCR analyses. With a decrease in CDK2 activity, trastuzumab decreased the kinase activity of cyclin E but had little effect on cyclin E protein level. Overexpression of wild-type cyclin E or its lower molecular weight forms did not influence the response to trastuzumab. Levels and activities of CDK6, cyclin A, and cyclin D1 were all suppressed by trastuzumab. As a result, trastuzumab inhibited Rb phosphorylation that associates with CDK2, cyclin E, CDK6, cyclin A, or cyclin D1. As predicted from these changes, trastuzumab decreased the DNA-binding activity of E2F, decreased the level of NPAT protein, and decreased the level of histone H4 mRNA. Blockade of the PI3K pathway with LY294002 produced similar effects to trastuzumab treatment on expression of each of these genes. Taken together, treatment of breast cancer cells that overexpress HER2 with the anti-HER2 antibody trastuzumab inhibits CDK2, Rb phosphorylation, E2F activity, NPAT, and histone H4 via PI3K signaling that are needed for both DNA and histone synthesis during progression from G(1) phase to S phase of the cell cycle.
[show abstract][hide abstract] ABSTRACT: Patients with locally recurrent breast cancer can also harbor regional nodal disease. Sentinel lymph node (LN; SLN) surgery is an accepted method for LN evaluation in early-stage breast cancer. We sought to evaluate the feasibility of SLN surgery in patients with locally recurrent breast cancer.
Patients undergoing SLN surgery at the time of treatment for recurrent breast cancer were identified. Clinical, pathologic, and operative details of initial and recurrent breast cancer events were analyzed.
From 2001 to 2005, 21 patients underwent SLN surgery for locally recurrent breast cancer. Previous breast procedures included segmental mastectomy in 17 patients and mastectomy in 4 patients. Previous axillary procedures included axillary LN dissection in 12 patients, SLN surgery in 5 patients, and no axillary surgery in 4 patients. Twelve patients had received breast irradiation. The SLN was identified and excised in 13 patients (62%). Six patients had drainage to nodal basins outside of the axilla (internal mammary and/or contralateral axilla). As the number of axillary nodes removed at primary surgery increased, the incidence of alternative lymphatic drainage increased: no previous axillary surgery, 0; 1-10 LNs removed, 30%; > 10 LNs removed, 50%.
Sentinel LN surgery is feasible in patients with locally recurrent breast cancer regardless of previous axillary node surgery or radiation. The incidence of alternative lymphatic drainage is increased in patients with > 10 axillary LNs removed at original operation or when radiation was part of the previous treatment. Sentinel LN surgery is a tool for guiding local-regional management of patients with locally recurrent breast cancer.
Clinical Breast Cancer 08/2006; 7(3):248-53. · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Few biologic markers have been studied as prognostic factors in recurrent rectal carcinoma patients. We sought to determine the influence of clinical, pathologic, and biologic (p53, bcl-2, and ki-67) variables on survival after curative resection of locally recurrent rectal cancer.
Retrospective review of patients with locally recurrent rectal cancer who received surgery with curative intent.
From 1988 to 1998, 134 patients with locally recurrent rectal cancer underwent operative exploration. Curative resection was performed in 85 patients. Median follow-up was 43 (range, 1.3-149) months. On multivariate analysis, negative predictors of overall survival included an elevated carcinoembryonic antigen level (P=0.02; hazard ratio 2.41; 95 percent confidence interval, 1.19-4.89) and an R1 resection margin (P = 0.01; hazard ratio, 2.81; 95 percent confidence interval, 1.27-6.21). In 26 patients for whom biologic variables were available, p53, bcl-2, and ki-67 did not significantly impact disease-specific survival or overall survival. Five-year disease-specific survival, overall survival, and pelvic control rates were 46, 36, and 51 percent respectively. Of the 50 patients who relapsed, time to second local recurrence was longer than time to development of metastasis (median, 16.5 vs. 9 months). Median survival for patients with metastatic recurrence was 26.l vs. 41.5 months for those with a subsequent local recurrence alone.
Approximately two-thirds of patients with locally recurrent rectal cancer can be resected for cure. Preoperative carcinoembryonic antigen and an R0 resection margin were the only significant predictors of overall survival. p53, bcl-2, and ki-67 did not impact survival outcomes.
Diseases of the Colon & Rectum 03/2006; 49(2):175-82. · 3.34 Impact Factor