Breast-conserving Operations Research Articles

Phyllodestumore der Brust

BACKGROUND: Phyllodes tumour is a very rare fibroepithelial neoplasia of the female breast. As a consequence of its low worldwide incidence of 0.3–1% of female breast tumours, the diagnosis, treatment, and prognosis of this disease are largely speculative and unresolved. A nationwide multicentre analysis was carried out with the objective of describing the diagnostic and therapeutic methods currently used and assessing the prognosis of this rare disease. METHODS: From April 2000 to June 2001 a computer-assisted survey was carried out in 24 surgical and gynaecological departments in Austria. Using a data sheet, the departments collected information on phyllodes tumours treated until present, as well as the follow-up care, treatment, and the long-term results. RESULTS: Across Austria 85 cases of women with phyllodes tumour covering the period from January 1985 to December 2000 were included in this study. In 40 (47%) cases the tumour was localised in the left breast, in 37 (44%) cases it was in the right breast. The histological review of the surgical specimens found that 28 (33%) patients had a malignant phyllodes tumour. Eight (9%) cases were borderline and 46 (54%) benign. The mean follow-up time was 39 (11–85) months. Seven patients died during the study. CONCLUSIONS: Patients with borderline and benign lesions should also undergo regular follow-up. A breast-conserving operation with adequate excision margins should be the primary objective, since even malignant tumours seldomly metastasise.

Histopathological and cell biological characteristics of ductal carcinoma in situ (DCIS) of the breast—a comparison between the primary DCIS and subsequent ipsilateral and contralateral tumours

The rate of ipsilateral local recurrence after ductal carcinoma in situ (DCIS) varies (between 5% and 30%) and depends on the type of operation (mastectomy vs. breast-conserving operation), and whether postoperative radiotherapy has been used. Ipsilateral local recurrence can either emanate from the primary lesion or be a new primary tumour. Contralateral lesions may also develop after DCIS. We compared histopathological and cell biological characteristics in 37 subsequent ipsilateral tumours (25 DCIS and 12 invasive cancers) and 13 subsequent contralateral invasive breast cancers with their corresponding primary DCIS. The histopathological parameters were re-evaluated and the cell biological factors were analysed using conventional immunohistochemical techniques in paraffin-embedded material. The concordance rate for high grade (nuclear grade 3) vs. non-high grade (nuclear grades 1+2) between the primary DCIS and the subsequent ipsilateral tumour was higher than between the primary DCIS and the subsequent contralateral invasive cancer (68% vs. 31%). Similar patterns in the concordance rates between the primary DCIS and ipsilateral vs. contralateral tumours were also found in the oestrogen receptor status (83% vs. 50%) and the progesterone receptor status (87% vs. 58%). The pattern persisted in the other factors examined (p53, c-erbB2, bcl-2 and Ki67), although it was less pronounced. The overall high rate of concordance in the characteristics between the primary DCIS and the subsequent ipsilateral tumours suggests that, in most cases, they represent true local recurrences. Subsequent contralateral tumours are more likely to be new primary cancers.

Risk factors for nipple involvement in breast cancer patients

AbstractIntroduction: A clinically normal‐appearing nipple in patients with breast cancer may contain unsuspected neoplastic cells. Preservation of a nipple containing occult malignancy could potentially increase local recurrence rates and affect disease‐free survival. Consequently, patients considered for breast conservation operations with nipple preservation must be carefully selected.Methods: Information available on 382 patients diagnosed and treated with breast cancer at the Clinical Center Nis from 2000 to 2003 were retrospectively reviewed. Multivariate hazard analyses was used to assess the association between potential risk factors of cancerous nipple involvement.Results: The frequency of nipple involvement was 12.04%. Nearly half of the patients had disease stage III and IV. Most patients, 29 (63.04%), had a tumor to nipple distance of less then 2 cm. Twenty‐five patients (54.34%) had more then four positive axillary nodes. A central/overlap tumor location was present in 28 (60.87%) patients. Cox multivariate analysis of prognostic factors showed that Stage III (RH 4.79 (1.50–14.68, 1.50–14.72); P= 0.008), central/overlap tumor location (RH 3.28 (0.90–11.20); P= 0.078) and nuclear grade III or greater (RH 2.26 (0.79 to 6.65); P= 0.065) had a statistically significant effect on malign nipple involvement.Conclusions: The multivariable model used in this study showed a significant association between stage, centrally located tumors and nuclear grade III or greater in predicting the risk of cancerous nipple involvement. Preoperative magnetic resonance imaging or computed tomography scan examinations are recommended for treatment planning of breast cancer, in particular nipple preserving surgery in patients with central/overlap tumor localization and with a tumor to nipple distance of less than 2 cm.

Surgical outcomes for clinically occult breast lesions: comparing radioguided occult lesion localisation (ROLL) vs. wire guided lumpectomy (WGL)

Background: Management of clinically occult breast lesions is still a major point of debate. Several techniques (eg, skin projection, guidewire localization) have been proposed, but all of them have technical limitations.Study Design: The aim of this study was to assess the efficacy of a new method to locate occult breast lesions using technetium-99m (99mTc)-labeled colloid particles of human serum albumin (radioguided occult lesion localization). We studied 647 consecutive patients (mean age 51.3 years; range 25 to 77 years) with nonpalpable breast lesions detected mammographically or by ultrasonography. Within 24 hours before operation, 3.7 MBq (0.1 mCi) of 99mTc-labeled colloid was injected directly into the center of the lesion using stereotactic mammographic guidance (when only microcalcifications were present) or ultrasonographic guidance (for opacities). Excision biopsy was performed with a gamma-detecting probe. After excision, the area was checked for residual radioactivity and the specimen was radiographed to verify complete removal of the lesion. The material was then sent for pathologic examination. The absorbed dose to the inoculated area and the external irradiation to staff were also determined.Results: In all 647 patients, the “hot spot” was located easily and quickly. X-ray and scintigraphy of the specimen verified the presence and centricity of the lesion in all patients but three (99.5%). Pathologic examination revealed 340 cancer lesions (52.6%). Of these patients, 339 (99.7%) were treated by breast-conserving operations and one (0.3%) received a modified radical mastectomy. No major surgical or postoperative complications were encountered. No recurrences were documented during follow-up. The absorbed dose to the breast and other tissue was negligible (0.03 ± 0.02 mGy/MBq), as was the dose to the surgeon’s hands (7.5 ± 5.0 μSv/h). The latter dose represents 0.015% and 0.002% of the recommended limits of the European Community for the general population and for exposed workers, respectively.Conclusions: Radioguided occult lesion localization seems to offer a simple and reliable method to locate occult breast lesions with a gamma-detecting probe, allowing complete removal of the lesion in 99.5% of patients. Because of the small quantity of radioactivity, the procedure is safe for both patients and medical staff.

Value of the Van Nuys Prognostic Index in prediction of recurrence of ductal carcinoma in situ after breast-conserving surgery.

The Van Nuys Prognostic Index (VNPI), an algorithm based on tumour size, tumour grade, presence of necrosis and excision margin width, is claimed to predict local recurrence after breast-conserving surgery for ductal carcinoma in situ (DCIS). The aim of this study was to examine the validity of the VNPI in a UK population. Clinicopathological data, including VNPI subgroups, for 237 patients who had breast-conserving operations for DCIS were examined. Multivariate data analysis was performed using a Cox regression model to examine the independence and relative importance of different variables in predicting recurrence, and to compare the data with those used in derivation of the VNPI. The median follow-up was 47 months. There were 37 ipsilateral local recurrences. Excision margin width (P < 0.001) and tumour grade (by Van Nuys grading (P = 0.014) or simple nuclear grading (P = 0.004)) were the only independent risk factors for local recurrence. Excision margin width had three times more power than grade in predicting local recurrence. Subgrouping data by VNPI score predicted recurrence-free survival (P < 0.001), but stratified 78 per cent of patients into a group with a moderate risk of local recurrence. Excision margin width is the most important predictor of local recurrence after breast-conserving surgery for DCIS. The VNPI lacked discriminatory power for guiding further patient management.

In vitro radiosensitivity measured in lymphocytes and fibroblasts by colony formation and comet assay: comparison with clinical acute reactions to radiotherapy in breast cancer patients

Purpose : To compare colony-forming and comet assays on fibroblasts and lymphocytes of 32 breast cancer patients irradiated after breast-conserving operations and to correlate the results with acute clinical radiation reactions in the skin. Material and methods : Skin fibroblasts were isolated and cultivated before radiotherapy and lymphocytes were drawn prior to the first and directly after the final external irradiation. The colony-forming assay was performed with fibroblasts and the comet assay with lymphocytes and fibroblasts of breast cancer patients according to standard protocols. The clinical radiation reactions of the patients were graded according to the RTOG system. Results : No significant correlation (p =0.09) was detected between clinical acute skin reactions and the in vitro clonogenic data in fibroblasts. Results of the comet assay in lymphocytes, however, showed a significant correlation (p <0.05) with the clinical data when patients were divided into two groups with average and elevated acute reactions. Apart from initial damage, fibroblasts did not show significant differences between the two patient groups. Repeated comet assays in lymphocytes of the same patient drawn before treatment and before and after external radiotherapy demonstrated good reproducibility of the test and no significant impact of preceding radiation treatment. There was a good correlation (r =0.65) between the comet assay results in fibroblasts and lymphocytes of the same individual. Conclusions : In this cohort of patients, a significant correlation between the in vitro results of the comet assay in lymphocytes and clinical acute reactions was detected. The results of the comet assay and of fibroblast colony formation did not correlate with in vitro radiosensitivity.

Use of technetium-99m–labeled colloid albumin for preoperative and intraoperative localization of nonpalpable breast lesions

Background: Management of clinically occult breast lesions is still a major point of debate. Several techniques (eg, skin projection, guidewire localization) have been proposed, but all of them have technical limitations. Study Design: The aim of this study was to assess the efficacy of a new method to locate occult breast lesions using technetium-99m ( 99mTc)-labeled colloid particles of human serum albumin (radioguided occult lesion localization). We studied 647 consecutive patients (mean age 51.3 years; range 25 to 77 years) with nonpalpable breast lesions detected mammographically or by ultrasonography. Within 24 hours before operation, 3.7 MBq (0.1 mCi) of 99mTc-labeled colloid was injected directly into the center of the lesion using stereotactic mammographic guidance (when only microcalcifications were present) or ultrasonographic guidance (for opacities). Excision biopsy was performed with a gamma-detecting probe. After excision, the area was checked for residual radioactivity and the specimen was radiographed to verify complete removal of the lesion. The material was then sent for pathologic examination. The absorbed dose to the inoculated area and the external irradiation to staff were also determined. Results: In all 647 patients, the “hot spot” was located easily and quickly. X-ray and scintigraphy of the specimen verified the presence and centricity of the lesion in all patients but three (99.5%). Pathologic examination revealed 340 cancer lesions (52.6%). Of these patients, 339 (99.7%) were treated by breast-conserving operations and one (0.3%) received a modified radical mastectomy. No major surgical or postoperative complications were encountered. No recurrences were documented during follow-up. The absorbed dose to the breast and other tissue was negligible (0.03 ± 0.02 mGy/MBq), as was the dose to the surgeon’s hands (7.5 ± 5.0 μSv/h). The latter dose represents 0.015% and 0.002% of the recommended limits of the European Community for the general population and for exposed workers, respectively. Conclusions: Radioguided occult lesion localization seems to offer a simple and reliable method to locate occult breast lesions with a gamma-detecting probe, allowing complete removal of the lesion in 99.5% of patients. Because of the small quantity of radioactivity, the procedure is safe for both patients and medical staff.

THE OPERATIVE MANAGEMENT OF SCREEN‐DETECTED BREAST CANCERS

Mammographic screening for breast cancer not only reduces the overall mortality from breast cancer but allows greater opportunities for breast-conserving operations. The predicted degree of breast conservation is not being realized, but is increasing in centres that have published their results. The operative management of breast cancers diagnosed by BreastScreen Central and Eastern Sydney Screening and Assessment Service were compared between two time periods: January 1988-December 1992 (group 1) and January 1993-December 1995 (group 2). The rate of breast conservation, and other data were compared between the two periods. An attempt was made with multivariate analysis to identify some of the factors that made mastectomy rather than conservation more likely. There were 723 cancers detected that were suitable for analysis (group 1, n = 273; group 2, n = 450). In group 1 the breast conservation rate was 42.9%; this increased significantly to 60.4% in group 2 (P < 0.001). The data were examined to determine if there was any other factor that had changed over the time periods which might account for the increased rate of breast conservation. The use of pre-operative diagnostic techniques such as fine needle aspirate cytology and core biopsy increased significantly. Multivariate analysis comparing the differences in patient age, diagnostic technique, tumour type, grade, size, location and lymph node status, both independently and compositely did not account for the increase in breast conservation in group 2. The increase in breast conservation is due to other factors such as the surgeons' approach and patient attitude. The use of pre-operative, minimally invasive tissue sampling techniques is increasing.

Combined Modality Approach for High-Risk Breast Cancer: The Milan Cancer Institute Experience

After 20 years of successive clinical trials, the results achieved at the Milan Cancer Institute have helped to establish the effectiveness of adjuvant combination chemotherapy in high-risk women with resectable breast cancer. The most significant findings can be summarized as follows: (1) the clinical benefit in terms of relapse-free and total survival can be prolonged up to 20 years from surgery; (2) the use of anthracyclines (doxorubicin) can contribute to improved treatment outcome; (3) dose intensity and dose size are the leading prognostic variables; and (4) adjuvant treatments are not associated with important iatrogenic morbidity. New modalities that could profoundly change current treatment strategies will involve high-dose sequential chemotherapy and primary chemotherapy. In fact, the use of rhG-CSF-elicited hematopoietic progenitors will grant a substantial reduction in granulocytopenia and related toxicities; this, in turn, will permit the administration of regimens based on high dose size and dose intensity. As far as primary chemotherapy is concerned, the shift from mutilating to breast-conserving operations has led to important advantages in a society concerned for body integrity. In the few studies with sufficient follow-up, objective tumor response to primary chemotherapy has been translated into superior relapse-free survival compared with that of nonresponders. In particular, from the first Milan study the knowledge is clearly emerging that the response rate is inversely related to the initial tumor volume and that the degree of tumor regression (complete pathologic remission versus moderate versus minimal response) appears to represent a marker of outcome. Should this crucial observation be confirmed in other ongoing trials, then the amount of tumor shrinkage could rank among the most important prognostic variables because it is reproducible and inexpensive. As a consequence, the achievement of complete (or near complete) pathologic remission will become the major goal of properly intensified drug regimens to ensure a durable relapse-free survival rate. To make legitimate the wide adoption of the strategy involving primary chemotherapy, most breast cancer specialists correctly advocate that the initial promising results be validated through classic randomized trials. The question to answer appears simple: Will preoperative chemotherapy be superior to postoperative chemotherapy in terms of relapse-free and total survival? In our opinion, the simple attempt to shift from postoperative (adjuvant) to preoperative (primary) chemotherapy may not be enough, although formally correct, to maximize treatment outcome, and thus become the new strategy of choice.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic contrast-enhanced and fat suppressed magnetic resonance imaging in suspected recurrent carcinoma of the breast: preliminary experience.

20 women with suspected recurrent breast cancer who had undergone previous breast-conserving operations were investigated using dynamic contrast-enhanced gradient echo (GRE) and fat suppressed spin echo (SE) magnetic resonance (MR) imaging. Histologically confirmed recurrent tumour was readily recognized on dynamic GRE scans by virtue of rapid, early and avid enhancement. Benign scars enhanced more slowly and reached lower magnitudes of enhancement. Fat suppressed SE images, which were typically acquired 10 min after contrast administration, were sensitive for the detection of tumour recurrence but lacked specificity. Early scanning after contrast administration offers the best prospects for distinguishing tumour recurrence from benign scarring. The criteria used to distinguish these two entities are highly dependent on the scan technique and the time at which images are obtained post-contrast.

Breast Cancer: Treatment Differences and Survival

To the Editor. —In a recent Editorial, Dr Baue1supported other authors and advocated breast-conservation operations and radiation therapy, "if the patient wishes this to be done." Neither in his Editorial nor in the references cited was there any mention of long-term adverse effects, complications, and increased morbidity and mortality from radiation therapy to the breast. Breast cancer has a long natural history. One should not compare mortality of treatment based on the first 5 years following treatment. In trials employing radical mastectomy with or without irradiation, Cuzick et al2found a significant excess of deaths after 10 years among patients given radiotherapy. Friedman3concluded from studying pathological tissues from 100 women who received radiation therapy that carcinoma of the breast cannot be considered a radiosensitive tumor. Yet radiation therapy must accompany breast-conservation operations. Modern radiotherapy for carcinoma of the breast irradiates a segment of the left

Breast Cancer: How to Mishandle Misconduct

At the end of January 1994,<i>JAMA</i>accepted an article by Lee-Feldstein et al¹on various prognostic factors related to survival of patients with breast cancer. These authors examined differences in operative approaches to breast cancer between types of hospitals and how mortality varied. Their data support the use of breast-conserving operations, a practice which they note is based largely on six randomized trials

Breast-conservation operations for treatment of cancer of the breast

Breast-conservation operations for treatment of cancer of the breast

Breast-Conservation Operations for Treatment of Cancer of the Breast

In this issue ofThe Journal, Lee-Feldstein et al¹report on the operative treatment and survival of patients with breast cancer categorized by the type and size of hospitals in which the therapy was performed. The authors conclude that a larger percentage of breast-conserving operations for small localized (negative axillary lymph nodes) or regional (positive axillary lymph nodes) cancers of the breast were done in teaching hospitals and a much lower percentage in small hospitals. The results of breast conservation were as good as the more radical operations. Local excision, lymph node dissection, and radiation therapy provided the best long-term results. Also, survival of patients with localized disease was significantly better at large community hospitals, compared with small hospitals, and was worse at health maintenance organization hospitals. Based on their observations and the recommendations of the National Institutes of Health (NIH) conference in 1990 on the treatment of early-stage

TUBULAR CARCINOMA OF THE BREAST-CLINICAL AND PATHOLOGICAL ANALYSIS OF 13 CASES-

Tubular carcinoma of the breast was employed as a new invasive histologic type in General Rule for Clinical and Pathological Record of Mammary Cancer in 1984. Among 1891 patients operated on for breast cancer at the department from 1972 to 1990, 13 cases (0.71%) had a tubular carcinoma. It has been reported that the tubular carcinoma grows at lower speed than that expected from its biological feature, and so it can be detected in a relatively small tumor; and lymph node involvement occurs in a low frequency. In this study the indication of breast-conserving operation which has been increasingly performed recently was investigated. These tubular carcinomas were histopathologically classified into pure-type (7 cases; 53.8%) which is almost occupied with 100%-tubular carcinoma element and mixed-type (6 cases; 46.2%) in which tubular carcinoma element coexists with other histologic type. As to their prognoses, one of 13 patients (7.7%) died of recurrence, but long survival was noted in all pure-type patients, though lymph node metastasis was observed. It is thought that the disease can be a possible candidate for breast-conserving operation.

Preoperative staging of breast cancer by palpation, mammography and high-resolution ultrasound.

In breast cancer preoperative determination of the tumor size is important for planning breast-conserving operations. In 100 patients with breast cancer, the preoperative tumor size was measured using clinical, mammographic and sonographic examinations and correlated with the results of a subsequent histological examination. Using a high-resolution real-time system, 98 tumors were visible. It was possible to detect not only early tumors under 1 cm in diameter, but also intraductal tumor components. This contributed greatly to the accuracy of the diagnosis. The sonographic measurement of tumor size demonstrated a correlation coefficient of 0.91 and was thus superior to mammography (0.79) and palpation (0.77). Measurement of the total tumor spread, including 39 multicentric lesions, showed an overestimation of 5% for the mammographic measurements and an overestimation of 4% for the sonographic measurements. Tumor extension was underestimated in 33% of the mammograms but in only 3% using ultrasound examination. The results, along with those of other studies, highlight the role of sonography in the diagnosis of breast cancer.

Significance of ipsilateral breast tumour recurrence after lumpectomy

Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on I BTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3·41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy.

Management of primary, operable breast cancer in Victoria

The study aimed to describe the surgical treatment in cases of primary, operable breast cancer in Victoria. All patients who were entered in a population-based cancer registry and who met the entry criteria over a six-month period were identified. In respect of each patient, the treating surgeon completed a questionnaire about patient characteristics, investigations, tumour description, surgery, radiotherapy and chemotherapy. For 716 eligible cases, 635 (89%) questionnaires were returned by 200 treating surgeons; this gave a mean rate of 6.3 breast-cancer patients per surgeon per year. Most (61%) surgeons treated one to four breast-cancer patients per year and only 4% of surgeons treated more than 20 breast-cancer patients each. Little systematic difference was found in the treatment approach that was adopted by the surgeons with heavy or light case-loads of patients with breast cancer. Twenty-two per cent of patients underwent breast-conserving operations. Virtually all the remainder underwent mastectomy, most commonly modified radical mastectomy.

The Changing Treatment of Breast Cancer

To Editor. — I am writing in regard to article by Mann et al 1 that reviews changing treatment of breast cancer in New Mexico during 14-year period. In this review, it is stated that the apparent lack of adjuvant radiotherapy in some women receiving conservative therapy may prove to be deleterious consequence of breast-conserving operations for treatment of breast cancer. When radiation therapy was not routinely given after partial or segmental mastectomy in this survey in New Mexico, it was believed by authors to be inadequate treatment. Two articles are quoted by authors to suggest that decreased survival occurs if radiation therapy is not given after all breast-conserving operations. One article that was referred to, that of Fisher et al, 2 reports a significantly decreased disease-free survival in patients undergoing segmental mastectomy alone compared with segmental mastectomy plus irradiation. Further reading

Changing Treatment of Breast Cancer in New Mexico From 1969 Through 1985

A review of information from the New Mexico Tumor Registry on women diagnosed as having primary breast cancer from 1969 through 1985 revealed temporal changes in the surgical treatment of this disease. After 1980 the percentage of women receiving breast-conserving surgery for local-stage disease increased from 6% to 25%. Most surgeons performing operations for breast cancer had not performed a breast-conserving operation before 1981 but had used this procedure at least once in the period from 1981 through 1985. Women younger than 50 years or older than 80 years were most likely to undergo this procedure. In that period, radiotherapy after breast-conserving surgery could not be documented for 26% of the women 65 years old or younger or for 56% of the women aged 65 years or older. Thus, there has been a marked shift in New Mexico in the surgical approach to local-stage breast cancer in the 1980s. This shift involved most surgeons treating the disease and included women of all age groups. The apparent lack of adjuvant radiotherapy in some women receiving conservative surgeries may prove to be a deleterious consequence of this change in surgical management.