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K J Van Zee

Publications and source records attributed to K J Van Zee.

At least 19 recordsLinked to original sources
PubMed2002

A prospective validated model for predicting axillary node metastases based on 2,000 sentinel node procedures: the role of tumour location [corrected].

AIMS: The purpose was to identify the independent predictive factors of axillary lymph-node metastases (ALNM) in infiltrating ductal carcinoma (IFDC) and to create a prospective, validated statistical model to predict the likelihood of ALNM in patients in the present era of sentinel lymph-node (SLN) biopsy and enhanced histopathology. METHODS: Univariate and multivariate analyses of 13 clinicopathological variables (including tumour location) were performed to determine predictors of ALNM in 1659 eligible SLN biopsy procedures. A logistic regression model was developed and then prospectively validated on a second population of 187 subsequent consecutive procedures. RESULTS: Age, pathological tumour size, palpability, lymphovascular invasion (LVI), histological grade, nuclear grade, ductal histological subtype, tumour location (quadrant) and multifocality were associated with ALNM in univariate analyses (P < 0.001). Of these, only palpability and histological grade were not statistically associated with ALNM in the multivariate analysis (P> 0.05). The frequency of ALNM in upper-inner-quadrant (UIQ) tumours was 20.6%, compared with 33.2% for all other quadrants (P<0.0005). There was no statistical difference between UIQ and other-quadrant tumours in any clinicopathological variables analysed. The logistic regression model, developed based on the population of 1659, had the same accuracy, sensitivity, specificity, positive predictive value and negative predictive value when applied prospectively to the second population. CONCLUSION: Tumour size, LVI, age, nuclear grade, histological subtype, multifocality and location in the breast were independent predictive factors for ALNM in IFDC. ALNM is less frequent in UIQ tumours than in other-quadrant tumours. Our prospectively validated predictive model could be valuable in pre-operative patient discussions, although staging of the axilla in the individual patient remains necessary.

Adult↗
PubMed2002

A selection algorithm for internal mammary sentinel lymph node biopsy in breast cancer.

Internal mammary lymph-node (IMN) metastases in breast carcinomas have a major influence on survival, comparable with the influence of axillary lymph-node metastases (ALNM). Prospective, randomized trials have demonstrated that complete IMN dissection as part of extended radical mastectomy does not improve overall or disease-free survival. In the subset of patients with tumours 1cm or less in size and no ALNM, information on IMN status would provide important information. In these cases, the presence of IMN metastases would change the staging from stage I to stage IIIB, according to the current tumour, node and metastasis classification. More importantly, it would influence these patients' adjuvant treatment. Lymphatic mapping for sentinel lymph-node (SLN) biopsy has demonstrated extra-axillary drainage in up to 35% of patients. Recent reports have demonstrated the feasibility of internal mammary sentinel lymph-node (IM-SLN) biopsy. Here we review the general prognostic and clinical significance of tumor location and lymph-node metastases in breast cancer and discuss the specific factors associated with IMN identification, metastases and treatment in the pre-SLN and SLN eras. Based on our review, we propose an algorithm for a selective approach to IM-SLN in breast cancer.

Algorithms↗
PubMed2001

Molecular analysis of the INK4A and INK4B gene loci in human breast cancer cell lines and primary carcinomas.

The INK4A and INK4B loci are located at 9p21 and have been implicated in the tumorigenesis of various human malignancies. The INK4A gene encodes two cell cycle regulators, p16(INK4A) and ARF, while INK4B encodes p15(INK4B). Previously, we have shown that the p16(INK4) tumor suppressor was not mutated or deleted in primary breast carcinomas. However, primary and metastatic breast carcinomas exhibited a relative hypomethylation of p16(INK4A), which is associated with expression, compared to normal breast tissue. The present study was conducted to determine if inactivation of p15(INK4B) and INK4A exon 1beta (ARF) are common events in breast carcinoma. Mutational analysis was performed by PCR-SSCP, and mRNA expression was evaluated by RT-PCR. Methylation-specific PCR was used to determine the methylation status of the p15(INK4B) promoter. Our results demonstrate that the p15(INK4B) gene was altered in 3 (21%) of the 14 breast cell lines; one had a silent mutation and two had homozygous deletion of the gene. None of the cell lines showed methylation of p15(INK4B). Two (14%) cell lines had homozygous deletion of INK4A exon 1beta. All normal and malignant breast tissue samples were wild-type and non-methylated for p15(INK4B) and wild-type for exon 1beta. Our results show that these structurally and functionally related genes are not invariably affected together, and the most frequently observed alteration at the INK4A and INK4B loci in breast carcinoma appears to be p16(INK4A) hypomethylation.

Blotting, Southern↗
PubMed2001

Expression of E2F-1 and E2F-4 is reduced in primary and metastatic breast carcinomas.

The E2F family of transcription factors can induce both cell proliferation and apoptosis. Whether they function as oncogenes or tumor suppressors appears to be tissue specific. Their role in breast carcinogenesis remains unclear. We found a decreased expression of E2F-1 and E2F-4 in 70% (7/10) of primary breast carcinomas and in all (10/10) metastatic nodal tissues when compared with the corresponding normal breast tissue. No tumor-specific mutation was detected, but polymorphisms were identified in E2F-1 exon 5 and in the polyserine tract of E2F-4. The presence of polymorphisms did not correlate with E2F expression. Among the 12 human breast cancer cell lines, one contained a missense mutation in E2F-1 exon 2. Five (42%) cell lines overexpressed E2F-1, while three (25%) expressed low levels of the protein. Our results suggest that not only are the E2Fs likely to function as tumor suppressors in breast cancer, but also that their down-regulation may be important in the development of metastases.

Adult↗
PubMed2001

Bracketing wires for preoperative breast needle localization.

OBJECTIVE: The purpose of this study was to evaluate the outcomes of bracketing wire placement during preoperative breast needle localization. SUBJECTS AND METHODS: We prospectively examined mammograms of 1057 consecutive lesions that had preoperative needle localization and surgical excision and classified the lesions according to Breast Imaging Reporting and Data System (BI-RADS) final assessment categories. Bracketing wires, defined as multiple wires placed to delineate the boundaries of a single lesion, were used in 103 (9.7%) of 1057 lesions. Medical records, imaging studies, and histologic findings in these 103 lesions were reviewed. RESULTS: Of 103 bracketed lesions, median lesion size was 3.5 cm (range, 1.5-9.5 cm). Ninety-three lesions (90.3%) contained calcifications; 65 lesions (63.1%) were BI-RADS category 5 (highly suggestive of malignancy); and 33 lesions (32.0%) were percutaneously proven cancers. The median number of wires placed was two (range, 2-5). Surgical histologic findings were carcinoma in 75 lesions (72.8%), atypical hyperplasia in eight lesions (7.8%), and benign in 20 lesions (19.4%). Of 42 calcific lesions that were bracketed and had postoperative mammograms available for review, complete removal of suspicious calcifications was accomplished in 34 (81.0%). Of 75 cancers that were bracketed, clear histologic margins of resection were obtained in 33 (44.0%). CONCLUSION: Bracketing wires were used during preoperative needle localization primarily for larger calcific lesions that were proven cancers or were highly suggestive of malignancy (BI-RADS category 5). Bracketing wires may assist the surgeon in achieving complete excision of calcifications, but bracketing wires do not ensure clear histologic margins of resection.

Adult↗
PubMed2001

Biological behavior of human breast cancer micrometastases.

PURPOSE: Clinically undetectable micrometastases may account for disease recurrence in breast cancer patients after variable disease-free intervals. However, little is known about the cellular mechanisms controlling human breast cancer micrometastases. We compared tumor proliferation rate, apoptotic index, and angiogenesis in human breast cancer micrometastases with those of macroscopic axillary lymph node metastases. EXPERIMENTAL DESIGN: Seven breast cancer micrometastases (<2 mm) obtained from the sentinel nodes of seven patients were compared with 13 macrometastases (lymph node replaced with tumor) obtained from 13 patients. The tissue was fixed in formalin, embedded in paraffin, serially sectioned, and evaluated by H&E and immunohistochemistry for cytokeratin. Tumor proliferation rate was assessed as the number of Ki-67-positive nuclei/total number of tumor nuclei. Tumor vascularity was quantified using antibody to factor VIII to identify microvessels per high-power field (at x400). Apoptosis was quantified using the terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling method. Results were analyzed with the Wilcoxon rank-sum test. RESULTS: Median size of micrometastases was 0.5 mm (range, 0.4-1.0), and the median number of tumor nuclei/section was 143 (range, 90-312). Median proliferation rate for macrometastases was greater than for micrometastases (35% versus 12%; P = 0.003). Median microvessel density/high-power field for macrometastases was greater than for micrometastases (17 versus 1; P < 0.001). There was no difference in apoptotic index between macrometastases and micrometastases (1.1% versus 0.7%; P = not significant). CONCLUSIONS: Human breast cancer micrometastases have lower tumor proliferation rates and angiogenesis than breast cancer macrometastases. These characteristics may explain their differential growth patterns.

Adult↗
PubMed2000

In microdissected ductal carcinoma in situ, HER-2/neu amplification, but not p53 mutation, is associated with high nuclear grade and comedo histology.

BACKGROUND: HER-2/neu and p53 are two molecular markers that have been the focus of investigation in patients with invasive breast carcinoma. However, most of the published data have relied on immunohistochemical detection of the proteins as a surrogate marker of the underlying genetic alterations, a detection method that often gives variable results due to technical factors. In addition, there are limited data documenting HER-2/neu amplification and p53 mutations in the various histologic subtypes of ductal carcinoma in situ (DCIS). The authors evaluated a series of microdissected, pure DCIS lesions comprising a spectrum of morphologic subtypes (comedo, micropapillary, papillary, cribriform, and solid) and their corresponding normal breast tissue for genetic aberrations in HER-2/neu and p53. METHODS: HER-2/neu amplification was determined by differential polymerase chain reaction, and p53 mutations were identified by single-strand conformation polymorphism analysis. RESULTS: HER-2/neu amplification was identified in 12 of 30 DCIS samples (40%), and p53 mutations were identified in 6 of 30 DCIS samples (20%). The genetic alterations were not present in any of the normal breast tissue samples. HER-2/neu amplification occurred predominantly in the comedo subtype (69% vs. 18% of the noncomedo subtype; P = 0.008) and in lesions of high nuclear grade (63% vs. 14% of low grade; P = 0.01). There was no difference in the frequency of p53 mutations among the subtypes or between low grade and high grade lesions. No correlation between the presence of the two genetic alterations was observed. CONCLUSIONS: The presence of HER-2/neu amplification, but not p53 mutations, correlates with histologic subtype and nuclear grade. The relatively frequent occurrence of HER-2/neu amplification and p53 mutations in DCIS tissue and their absence in normal breast tissue suggest that these genetic aberrations are important early in breast duct carcinogenesis.

Breast Neoplasms↗
PubMed2000

Magnetic resonance imaging facilitates breast conservation for occult breast cancer.

INTRODUCTION: Occult primary breast cancer, i.e., isolated axillary adenocarcinoma without detectable tumor in the breast by either physical exam or mammography, represents up to 1% of operable breast cancer. Modified radical mastectomy (MRM) is generally the accepted treatment for this condition although tumor is identified in only two-thirds of mastectomy specimens. Breast magnetic resonance imaging (MRI) can identify occult breast carcinoma and may direct therapy. This study examined the ability of breast MRI to detect occult breast cancer and to facilitate breast conservation therapy. METHODS: Forty women with biopsy-proven metastatic adenocarcinoma to an axillary lymph node and no evidence of primary cancer were studied. All patients had a physical examination, mammography, and MRI of the breast. Using a dedicated breast coil, MRI imaging was performed with and without gadolinium enhancement. Positive MRI scans were compared with histopathologic findings at the time of operation (n = 21). RESULTS: MRI identified the primary breast lesion in 28 of 40 women (70%). Of these 28 patients, 11 had MRM, 11 had lumpectomy/axillary lymph node dissection (ALND)/radiotherapy (XRT), 2 had ALND/XRT alone, and 4 had no local treatment secondary to stage IV disease. Two women initially treated with lumpectomy/ALND subsequently had mastectomy for positive margins. Of the women with positive MRI who had breast surgery, 21 of 22 (95%) had tumor within the surgical specimen. Twelve women had negative MRI of the breast. Five of these 12 underwent MRM, of whom 4 had no tumor in the mastectomy specimen. The remaining 7 patients had ALND and whole breast radiation (ALND/XRT) (n = 5), or were observed (n = 2). Overall, 18 of 34 women surgically treated had MRM, while 16 (47%) preserved their breast. Tumor yield for patients having breast surgery was 81%. CONCLUSIONS: MRI of the breast can identify occult breast cancer in many patients and may facilitate breast conservation in select women. Negative breast MRI predicts low tumor yield at mastectomy.

Adenocarcinoma↗
PubMed2000

Sentinel lymph node biopsy: is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?

BACKGROUND: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to determine the incidence of sentinel node metastases in patients with high-risk ductal carcinoma-in-situ (DCIS) and DCIS with microinvasion (DCISM). METHODS: From November 1997 to November 1999, all patients who underwent sentinel node biopsy for high-risk DCIS (n = 76) or DCISM (n = 31) were enrolled prospectively in our database. Patients with DCIS were considered high risk and were selected for sentinel lymph node biopsy if there was concern that an invasive component would be identified in the specimen obtained during the definitive surgery. Patients underwent intraoperative mapping that used both blue dye and radionuclide. Excised sentinel nodes were serially sectioned and were examined by hematoxylin and eosin and by immunohistochemistry. RESULTS: Of 76 patients with high-risk DCIS, 9 (12%) had positive sentinel nodes; 7 of 9 patients were positive for micrometastases only. Of 31 patients with DCISM, 3 (10%) had positive sentinel nodes. 2 of 3 were positive for micrometastases only. Six of nine patients with DCIS and three of three with DCISM and positive sentinel nodes had completion axillary dissection; one patient with DCIS had an additional positive node detected by conventional histological analysis. CONCLUSIONS: This study documents a high incidence of lymph node micrometastases as detected by sentinel node biopsy in patients with high-risk DCIS and DCISM. Although the biological significance of breast cancer micrometastases remains unclear at this time, these findings suggest that sentinel node biopsy should be considered in patients with high-risk DCIS and DCISM.

Adult↗
PubMed2000

Sentinel lymphadenectomy accurately predicts nodal status in T2 breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has emerged as a reliable, accurate method of staging the axilla for early breast cancer. Although widely accepted for T1 lesions, its use in larger tumors remains controversial. This study was undertaken to define the role of SLNB for T2 breast cancer. STUDY DESIGN: From a prospective breast sentinel lymph node database of 1,627 patients accrued between September 1996 and November 1999, we identified 223 patients with clinical T1-2N0 breast cancer who underwent 224 lymphatic mapping procedures and SLNB followed by a standard axillary lymph node dissection (ALND). Preoperative lymphatic mapping was performed by injection of unfiltered technetium 99 sulfur colloid and isosulfan blue dye. Data about patient and tumor characteristics and the status of the sentinel lymph nodes and the axillary nodes were analyzed. Statistics were performed using Fisher's exact test. RESULTS: Two hundred four of 224 sentinel lymph node mapping procedures (91%) were successful. Median tumor size was 2.0 cm (range 0.2 to 4.8 cm). One hundred forty-five of the 204 patients had T1 lesions and 59 patients had T2 lesions. There were 92 pathologically positive axillae, 5 (5%) of which were not evident either by SLNB or by intraoperative clinical examination. The false-negative rate and accuracy were not significantly different between the two groups, but axillary node metastases were observed more frequently with T2 than with T1 tumors (p = 0.005); other factors, including patient age, prior surgical biopsy, upper-outer quadrant tumor location, and tumor lymphovascular invasion were not associated with a higher incidence of false-negative SLNB in either T1 or T2 tumors. CONCLUSIONS: SLNB is as accurate for T2 tumors as it is for T1 tumors. Because no tumor or patient characteristics predict a high false-negative rate, all patients with T1-2N0 breast cancer should be considered candidates for the procedure. Complete clinical examination of the axilla should be undertaken to avoid missing palpable axillary nodal metastases.

Adult↗
PubMed2000

Evaluation of pectoralis major muscle in patients with posterior breast tumors on breast MR images: early experience.

PURPOSE: To evaluate the ability to use breast magnetic resonance (MR) imaging to assess disease extent in patients with posterior breast masses who are suspected to have tumor invasion into underlying muscle. MATERIALS AND METHODS: Nineteen patients with posterior breast masses underwent three-dimensional, gradient-echo, 1.5-T MR imaging before and after the administration of gadopentetate dimeglumine. Thirteen had deep palpable masses that were clinically determined to be fixed to the underlying chest wall. Twelve had mammographic findings that caused muscle involvement to be suspected, and seven had normal mammograms. All patients underwent surgery. MR images were reviewed and were correlated with histologic findings. RESULTS: Enhancing masses were identified on MR images in all 19 patients. Five (26%) of the 19 patients had masses that abutted the muscles, with obliteration of the fat plane and muscle enhancement. All five had muscle involvement at surgery. In the remaining 14 (74%) patients, no enhancement of muscle was seen; none of these had invasion of the muscle at surgery. CONCLUSION: Extension of adjacent tumor into underlying musculature was indicated by abnormal enhancement within these structures. Violation of the fat plane between tumor and muscle, without other findings, did not indicate tumor involvement of these deep structures.

Adult↗
PubMed1999

Long term follow-up of women with ductal carcinoma in situ treated with breast-conserving surgery: the effect of age.

BACKGROUND: Although in recent years there has been a dramatic increase in both the incidence of ductal carcinoma in situ (DCIS) and breast-conserving therapy for patients who have this disease, the optimal treatment for these patients remains controversial. Most data regarding outcomes have come from small, retrospective studies, with little data published from prospective, randomized studies. This study investigates the effects of age, postoperative breast irradiation, and other factors on local relapse free survival after breast-conserving surgery for women with DCIS in a large, single-institution series. METHODS: A review was performed of all patients with DCIS who underwent breast-conserving surgery at Memorial Sloan-Kettering Cancer Center from 1978 through 1990. Of the 171 cases identified, data on follow-up and radiation therapy were available for 157. All available pathology slides (132 of 157) were rereviewed to determine histologic subtype, nuclear grade, presence of necrosis, and microscopic tumor size. Sixty-five patients (41%) received postoperative radiation therapy; selection criteria evolved over the time period. The median follow-up was 74 months. RESULTS: Factors that were significantly (P< or =0.05) associated with a lower recurrence rate were older age, noncomedo subtype, lower nuclear grade, negative margins, and postoperative radiation therapy. The 6-year actuarial recurrence rate was 9.6% for patients who received postoperative radiation therapy and 20.7% for patients who had excision only (P = 0.05). Comparison of patients of ages > or =70, 40-69, and <40 years revealed a significantly lower risk of recurrence with increasing age. Actuarial 6-year local relapse rates were 10.8%, 14.0%, and 47.2%, respectively (P = 0.047). A benefit from radiation therapy was suggested for each age group. There was no statistically significant correlation between age group and any histologic factor examined. In multivariate analysis, only margin status was statistically significant (P = 0.05). CONCLUSIONS: In addition to margin status, pathologic factors, and the use of radiation therapy, age is another factor that should be considered in assessing the risk of local recurrence after breast-conserving surgery for patients with DCIS.

Adult↗
PubMed1999

Issues of regret in women with contralateral prophylactic mastectomies.

BACKGROUND: Patients with a history of carcinoma of one breast have an estimated risk of 0.5% to 0.75% per year of developing a contralateral breast cancer. This risk prompts many women to consider contralateral prophylactic mastectomy (CPM) as a preventive measure. Virtually nothing is known about patient acceptance following CPM. We have developed a National Prophylactic Mastectomy Registry comprised of a volunteer population of 817 women from 43 states who have undergone prophylactic (unilateral or bilateral) mastectomy. METHODS: Of the 346 women with CPM who responded to national notices, 296 women returned detailed questionnaires. The information obtained included patient demographics, family history, reproductive history, ipsilateral breast cancer staging and treatment, as well as issues involving the CPM. RESULTS: At median follow-up of 4.9 years, the respondents were primarily married (79%), white (97%) women who had some level of college education or above (81%). These women cited the following reasons for choosing CPM: (1) physician advice regarding the high risk of developing contralateral breast cancer (30%); (2) fear of developing more breast cancer (14%); (3) desire for cosmetic symmetry (10%); (4) family history (7%); (5) fibrocystic breast disease (4%); (6) a combination of all of these reasons (32%); (7) other (2%); and (8) unknown (1%). Eighteen of the 296 women (6%) expressed regrets regarding their decision to undergo CPM. Unlike women with bilateral prophylactic mastectomies, regrets tended to be less common in the women with whom the discussion of CPM had been initiated by their physician (5%) than in the women who had initiated the discussion themselves (8%) (P = ns). Family history and stage of index lesion had no impact on regret status. The reasons for regret included: (1) poor cosmetic result, either of the CPM or of the reconstruction (39%); (2) diminished sense of sexuality (22%); (3) lack of education regarding alternative surveillance methods or CPM efficacy (22%); and (4) other reasons (17%). CONCLUSIONS: To minimize the risk of regrets in women contemplating CPM, it is imperative that these women be counseled regarding an estimation of contralateral breast cancer risk, the alternatives to CPM, and the efficacy of CPM. In addition, these women should have realistic expectations of the cosmetic outcomes of surgery and understand the potential impact on their body image.

Adult↗
PubMed1999

Six-year follow-up of patients with microinvasive, T1a, and T1b breast carcinoma.

BACKGROUND: Management of patients with breast cancers < or = 1 cm remains controversial. Reports of infrequent nodal metastases in tumors < or = 5 mm has led to suggestions that axillary dissection should be selective, and that tumor characteristics should guide adjuvant therapy. METHODS: A retrospective review of 290 patients with breast cancer 1 cm in size or smaller from 1989 to 1991 was done. Distant disease-free survival (DDFS) was the primary outcome measure. RESULTS: There were 95 T1a (< or = 5 mm) and 196 T1b (6-10 mm) cancers. Nodal metastases were found in 8 T1a and 26 T1b tumors. Larger size, poorer differentiation, and lymphovascular invasion (LVI) were associated with more nodal metastases, but none of these trends reached statistical significance. The 6-year DDFS was 93% for node-negative and 87% for node-positive patients (P = .02). Overall, breast cancers with poorer differentiation and LVI trended toward a poorer outcome. For patients with node-negative tumors, LVI was associated with a poorer outcome (P = .03). The size of the primary tumor was not predictive of outcome. There were no nodal metastases or recurrences in the 18 patients with microinvasive breast cancer. CONCLUSIONS: Lymph node status is the major determinant of outcome in breast cancers 1 cm in size or smaller. Accurate axillary assessment remains crucial in management of small breast cancer.

Adult↗
PubMed1998

Hypomethylation and increased gene expression of p16INK4a in primary and metastatic breast carcinoma as compared to normal breast tissue.

Controversy continues to surround the role of p16INK4a in cell cycle control and carcinogenesis. Mutations, deletions and changes in methylation patterns of p16INK4a have been proposed as mechanisms leading to abnormal expression of the gene. We show here that primary and metastatic breast carcinomas demonstrate hypomethylation of p16INK4a which is associated with expression of p16INK4a mRNA, as compared to normal breast tissue which demonstrates a relative hypermethylation of p16INK4a associated with the absence of p16INK4a expression. These data suggest that methylation and lack of expression of p16INK4a is not a central mechanism in the development of breast carcinoma, but rather that the gene is functioning and expressed in breast carcinoma more frequently than in normal breast tissue. The role of p16INK4a is much more complex than has been previously hypothesized.

Breast↗