Interstitial laser therapy of breast fibroadenomas with 6 and 8 year follow-up.

Fibroadenomas are non-cancerous breast tumors commonly seen in teenagers but also found in women at the time of first mammogram. They have distinct physical findings and imaging features but the definitive diagnosis is made by ultrasound or stereotactic guided needle biopsy. Treatment options are observation or surgical removal. Recently, removal by ultrasound-guided technique has been reported. Alternatively, the tumor may be ablated within the breast by cold (cryotherapy) or by heat (laser, radiofrequency, focused ultrasound and microwave). In this paper the laser treatment in two patients, one with bilateral fibroadenomas, with 6 and 8 year follow-up is presented.

Thermal ablation of the goat mammary gland as a model for post-lumpectomy treatment of breast cancer: preliminary observations.

BACKGROUND: Partial breast irradiation post-lumpectomy, with a balloon bearing a radioactive source in its center, is practiced as an alternative to whole breast irradiation in the treatment of breast cancer. The goal is to ablate residual malignant cells within 1 cm radius of the resected lumpectomy margin. We hypothesize that this goal may be achieved with a fluid-filled heated balloon. METHODS: Nubian-cross goats were treated under general anesthesia. The two mammary glands were sequentially bisected and a non-inflated balloon with a heating element was placed in the center of the gland which was re-sutured. Two series of experiments were conducted. In the first 22 goats (44 glands), the balloon was inflated with 5% dextrose to a pressure of 150 mmHg and heated at 87 degrees C over selected time intervals of 1-24 minutes. In the second series (16 glands), the re-programmed device operated at 50-80 mmHg over selected time intervals of 5-20 minutes. The depth of necrosis was histologically determined after sacrificing the goats and excising the glands. RESULTS: In the first series, glandular necrosis was noted to extend to a depth of 3.2-9.6 mm for the above heating cycles. Corresponding figures for the second series ranged from 4.7-8.6 mm for treatment times of one minute 'warm up' to 20 minutes of heating at 90 degrees C. The animals exhibited no systemic side effects post-treatment. CONCLUSION: An experimental model describing a thermal technique causing necrosis of the goat mammary gland is described.

Image-guided surgery of small breast cancers.

BACKGROUND: Widespread screening mammography has resulted in detection of many breast cancers smaller than one cm. Image-guided percutaneous needle sampling provides accurate diagnostic and prognostic information for adjuvant therapy. Less invasive methods based on imaging techniques are emerging as an alternative to wire localization and lumpectomy. DATA SOURCES: Information presented in this overview was provided by seven investigators from five medical centers in the United States. These researchers are currently developing various techniques of image-guided percutaneous therapy of small (Tis, 1) breast cancers. CONCLUSIONS: Several percutaneous treatment modalities for treatment of early breast cancer, either excisional or in-situ ablative, are described in this overview and their potential applications are discussed.

Occult metastases in sentinel nodes of 200 patients with operable breast cancer.

BACKGROUND: Up to 30% of patients with operable breast cancer and negative regional lymph nodes experience disease recurrence within 10 years. Serial sectioning and immunohistochemical staining of these nodes have revealed 9% to 30% occult metastases. METHODS: Sentinel nodes from 200 patients with T1 and T2 invasive breast carcinoma were step-sectioned at 2- to 3-mm intervals, fixed in 10% formalin, and embedded in paraffin. Sections were taken from the face of the blocks and stained with hematoxylin and eosin (H&E). The blocks were then cut completely, and sections at .25-mm intervals were stained with cytokeratin and examined. RESULTS: Tumor metastases were found in 34 patients when the sentinel nodes were examined at 2- to 3-mm intervals and in an additional 51 patients when the nodes were sectioned in their entirety at .25-mm intervals and stained with cytokeratin, bringing the total number of patients with metastases to 85. Of the 51 patients whose metastases were detected by 2- to 3-mm sectioning and cytokeratin staining, 27 had isolated tumor cells and 24 had clusters of innumerable malignant cells, all of which were visualized and confirmed by H&E staining of the adjacent sections. CONCLUSIONS: Histologic examination of sentinel nodes of patients with invasive breast cancer sectioned at 2- to 3-mm intervals and stained with H&E significantly underestimates nodal metastases. Sectioning of the entire sentinel nodes at .25-mm intervals and staining with cytokeratin detects metastases as either isolated cells or as clusters.

Stereotactically guided laser therapy of occult breast tumors: work-in-progress report.

HYPOTHESIS: Mammographically detected breast tumors can be completely ablated with laser energy. DESIGN: Nonrandomized control trial. SETTING: A university hospital ambulatory care center. PATIENTS: Thirty-six patients with mammographically detected well-defined breast tumors were selected. INTERVENTIONS: The diagnosis of malignant neoplasms and determination of prognostic factors were established by image-guided needle-core biopsy. Patients were treated on a stereotactic table, using a 16- to 18-gauge laser probe, with an optic fiber transmitting a predetermined amount of laser energy. A multisensor thermal probe was inserted into the breast adjacent to the laser probe to monitor treatment. In the last 10 patients, the tumor blood flow was evaluated before and after laser therapy with contrast-enhanced color Doppler ultrasound. One to 8 weeks after laser therapy, the tumors were surgically removed and serially sectioned. MAIN OUTCOME MEASURE: Complete necrosis in 66% of tumors. RESULTS: Total tumor ablation with negative margins was observed whenever 2500 J/mL of tumor was given or the thermal sensors recorded 60 degrees C. Microscopic examination at 1 week showed disintegration of malignant cells, with peripheral acute inflammatory response and at 4 to 8 weeks extensive fibrosis. Contrast-enhanced color Doppler ultrasound revealed loss of tumor circulation after therapy, and positron emission tomography scan correlated well with histologic findings. There were no systemic adverse effects. Two patients sustained 3 x 4-mm skin burns around the laser needle. CONCLUSION: A stereotactically guided minimally invasive technique may be effective for the treatment of mammographically detected breast cancer.

Positron emission tomography with fluorine-18 fluorodeoxyglucose to evaluate response of early breast carcinoma treated with stereotaxic interstitial laser therapy.

Stereotaxic interstitial laser therapy is a promising new alternative to surgery to treat early-stage breast cancer. With this, laser energy coagulates the tumor with controlled heat, leading to fibrosis. Fluorodeoxyglucose positron emission tomography (FDG PET) scanning was performed in four patients treated by this technique to determine the degree of necrosis after interstitial laser therapy. The results showed that FDG PET scanning was in close agreement with histopathologic findings, confirming complete necrosis in one patient and variable response in the other three patients. Uptake of FDG appears to be a reliable means to monitor treatment response after interstitial laser therapy and may be useful in the management of breast cancer when used with this new procedure.

Occult metastases in the sentinel lymph nodes of patients with early stage breast carcinoma: A preliminary study.

BACKGROUND: Thirty percent of lymph node negative patients with operable breast carcinoma experience disease recurrence within 10 years. Retrospective serial sectioning of axillary lymph nodes has revealed undetected metastases in 9-30% of these patients. These occult metastases have been shown to have an adverse effect on survival. Serial sectioning (SS) is impractical for all axillary lymph nodes harvested from Levels I and II, but it is feasible if applied only to sentinel lymph nodes. METHODS: Sentinel lymph nodes from 52 patients with invasive breast carcinoma were cut at 2 mm intervals, fixed in 10% formalin, and embedded in paraffin. Sections were taken from the blocks, stained with hematoxylin and eosin (H & E), and compared with cytokeratin-stained sections taken at 0.25 mm intervals throughout the entire blocks. RESULTS: Tumor metastases were found in 6 patients (12%) when the sentinel lymph nodes were sectioned at 2 mm intervals and stained with H & E, compared with 30 patients (58%) when the same lymph nodes were serially sectioned at 0.25 mm intervals and stained with cytokeratin. Of 24 patients whose metastases were detected by SS and cytokeratin staining, 12 had isolated tumor cells and 12 had colonies of several thousand malignant cells. CONCLUSIONS: Routine histologic examination of axillary lymph nodes, including sentinel lymph nodes, in cases of breast carcinoma significantly underestimates lymph node metastases. This deficiency may be overcome by SS of the entire lymph nodes and staining with a specific monoclonal antibody. The percentage of patients found to have colonies of cells that were missed by routine sectioning corresponds closely to the percentage of "lymph node negative" patients who would be expected to relapse. The true clinical significance of these occult metastases will be determined by long term follow-up. [See editorial on pages 905-7, this issue.]

Sentinel node biopsy in the staging of breast cancer.

BACKGROUND: The role of axillary lymph node dissection (ALND) in breast cancer is currently being reevaluated. Sentinel node biopsy (SNB) holds promise for replacing full dissection in a large number of patients with breast cancer. MATERIALS: We evaluated SNB utilizing an intraoperative gamma probe localization technique following injection of technetium sulfur colloid in 80 patients with primary breast cancer and clinically negative axillae. Forty-eight patients were evaluated at Baptist Medical Center, Montgomery, Alabama, and 32 at Rush-Presbyterian-St. Luke's Medical Center in Chicago, Illinois. RESULTS: At least one sentinel node was found in 70 of the 80 patients (88%). One patient had a sentinel node in both the axilla and internal mammary chain. The remainder had axillary sentinel nodes only. The sentinel nodes accurately predicted the status of the axilla in 69 of the 70 patients (99%). One of 14 node-positive patients would have been missed with sentinel node biopsy alone, for a false negative rate of 7%. Four node-positive patients would have been missed with routine ALND without serial sectioning (SS) and immunohistochemical staining (IH) of the sentinel node. CONCLUSIONS: Sentinel node biopsy with SS and IH more precisely predicted the status of the axilla than routine ALND in this group of patients. SNB will likely replace full axillary dissection in the majority of patients with breast cancer.

Serial sectioning of sentinel nodes in patients with breast cancer: a pilot study.

BACKGROUND: Recent reports indicate that the sentinel node, defined as the first regional lymph node to receive lymphatic fluid from the breast, accurately represents the metastatic status of the primary breast cancer. However, routine single section examination of the regional nodes, including the sentinel node, underestimates the true incidence of metastases. The goal of this study is to determine whether multiple sectioning of sentinel nodes will detect occult metastases in operable breast cancer. METHODS: Nineteen patients with invasive breast cancers were injected with technetium-99m sulfur colloid solution around the tumor or at the biopsy site before lumpectomy and axillary lymph node dissection (ALND) or mastectomy. The labeled sentinel lymph nodes (SLND) were bivalved, and a central section was taken for hematoxylin and eosin (H & E) examination. The sentinel nodes of 13 patients, which were reported to be negative for metastases, were serially sectioned at 0.5-mm intervals and stained with H & E and a cytokeratin stain, CAM 5.2. RESULTS: In the 13 node-negative patients, occult metastases were found in the sentinel nodes of 3 patients (23%). Two were seen on H & E and one by cytokeratin stain. The mean numbers of SLND and ALND in this series were 2.6 and 12.5, respectively, and the average number of sections for the two groups was 14 and 1, respectively. CONCLUSION: Multiple sectioning of the sentinel node or nodes detects occult metastases and changes the staging of breast cancer.

Utilization of core wash material in the diagnosis of breast lesions by stereotactic needle biopsy.

BACKGROUND: Several reports have compared the results of fine-needle aspiration and stereotactic core needle biopsy in nonpalpable breast lesions. In this study the authors describe a simple method to retrieve cytologic material from a core breast biopsy sample that provides the diagnosis within 1 hour of the procedure. METHODS: Two hundred and eleven nonpalpable breast lesions were biopsied. Each core needle biopsy sample was placed in a mesh bag, and the bag and needle notch were washed in Cytolyt solution to obtain a monolayer using a commercial ThinPrep processor. The cytologic diagnoses were divided into four categories: benign, suspicious, malignant, and unsatisfactory, which then were compared with core needle biopsy results. RESULTS: Cytology reports of 211 lesions were as follows: 169 lesions (80%) were benign, 16 lesions (7.6%) were suspicious, 11 lesions (5.2%) were malignant, and 15 lesions (7.1%) were unsatisfactory. Core needle biopsy showed 165 of 169 samples (98%) to be benign and 4 to be malignant. Of the 16 suspicious smears, 10 were invasive carcinoma, 2 were in situ lesions, 3 were hyperplasias, and 1 was fibrosis. Of the 11 malignant smears, 10 were confirmed on core needle biopsy and 1 was read as atypia on the first core needle biopsy sample and malignant on a second, separate, follow-up core needle biopsy. Of the 15 unsatisfactory samples, 14 were found to be benign and 1 was found to be malignant on a separate, follow-up core needle biopsy. CONCLUSIONS: The core wash technique was 85% sensitive and 98% specific for malignancy. Only 7% of specimens were insufficient for diagnosis, and 93% of these were proven to be benign. This technique is useful for immediate (within 1 hour) diagnosis of breast lesions, alleviating patient anxiety and supplementing the diagnostic yield of the core biopsy.

Lymph node micrometastases from breast carcinoma: reviewing the dilemma.

BACKGROUND: The presence or absence of regional lymph node metastases has been one of the most important determining factors in recommending adjuvant chemotherapy for patients with breast carcinoma. However, because of the 15-20% failure rate at 5 years for lymph node negative patients, other tumor-related prognostic factors have gained greater significance in this decision-making process. Many investigators have reported finding micrometastases that were not detected by routine sectioning of the lymph nodes but were identified by multiple sectioning and additional staining. This review attempts to evaluate the role of occult lymph node micrometastases and their relevance to disease recurrence. METHODS: A literature search of the entire MEDLINE data base was conducted. All relevant articles were reviewed for the criteria they used to define micrometastases. The frequency of detection of micrometastases by various methodologies and the prognostic significance of such deposits were examined. RESULTS: Tumor deposits involving the lymph nodes were found to be arbitrarily categorized as either micrometastases or macrometastases, with the cutoff point ranging from 0.2-2.0 mm. The detection rate of such deposits by conventional techniques was inadequate. Serial sectioning and immunohistochemistry appeared to increase the detection rate by 9-33%. A definite survival disadvantage was noted for patients with such occult metastases. CONCLUSIONS: Current routine histologic examination of regional lymph nodes underestimates breast carcinoma metastases. Serial sectioning and immunohistochemistry increase the yield but are too labor-intensive and expensive for routine use. However, the introduction of the sentinel lymph node biopsy in lieu of axillary lymph node dissection in cases of breast carcinoma holds promise for making these methods practical and cost-effective.

Stereotactic core-needle biopsy of the breast: a report of the Joint Task Force of the American College of Radiology, American College of Surgeons, and College of American Pathologists.

A national task force consisting of members from the American College of Radiology, the American College of Surgeons, and the College of American Pathologists examined the issues surrounding stereotactic core-needle biopsy for occult breast lesions. Their report includes indications and contraindications, informed consent, specimen handling, and management of indeterminate, atypical, or discordant lesions.

Cryosurgery of breast cancer.

OBJECTIVE: To determine the feasibility and efficacy of cryosurgery of breast cancer. DESIGN: In phase 1, carcinogen-induced mammary adenocarcinomas in 13 Sprague-Dawley rats were treated by cryosurgery and were then examined for histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50 DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor temperatures, and duration and number of freeze-thaw cycles on tumor viability. In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the breasts of 4 dogs and 4 sheep. These animals were followed up for procedure-related complications; the histopathologic necrosis of the cryolesions were correlated with the ultrasound images. Based on the results of these experiments, ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical trial. RESULTS: In phase 1, a single, short-term (< 7 minutes) freeze killed only tumors smaller than 1.5 cm in diameter, despite an apparent decrease to -40 degrees C at the periphery of each tumor. In phase 2, varying the peripheral tumor temperature to as low as -70 degrees C, using a single, short-term (< 7 minutes) freeze did not alter the results from phase 1. If the ice ball fully encompassed the tumor, however, maintaining it for at least 15 minutes achieved 100% tumor kill independent of tumor size. In phase 3, creation of a reproducible ultrasound-monitored cryolesion was facilitated when 2 freeze-thaw cycles were performed. No procedure-related complications were noted. In the human trial, 2 invasive lobular carcinomas from 1 patient were treated by cryosurgery and were negative for persistent tumor by core needle biopsy performed 4 and 12 weeks after a well-tolerated procedure. CONCLUSIONS: In situ breast cryosurgery has been proved to be feasible and efficacious in small and large animal studies and has been successfully performed in 1 patient with breast cancer. The results of this study suggest that ultrasound-guided cryosurgery of breast cancer warrants further investigation.

Axillary node status in nonpalpable breast cancer.

BACKGROUND: The metastatic status of the axillary nodes is prognostically important but its value has been questioned in the management of nonpalpable breast tumors. This study correlates the incidence of positive nodes with the size of the primary nonpalpable tumors. METHODS: We retrospectively analyzed 220 invasive and 21 microinvasive breast cancers that were excised after needle localization and for which axillary dissections were subsequently performed. Of invasive cancers, 166 presented as mass lesions with or without microcalcifications and 54 as microcalcifications alone. The size of the mass lesions (n = 166) was determined mammographically and on pathologic specimens. They were subdivided into five groups according to diameter: (a) < or = 5 mm, (b) 6-10 mm, (c) 11-20 mm, (d) > 20 mm, and (e) unrecorded size. RESULTS: Axillary metastases were found in 9% of patients whose cancer presented as microcalcifications alone. They were found in 0, 11, and 22% of patients in mammographic groups, a, b, and c, respectively. In the corresponding groups in which size was determined from the pathology report, metastases were found in 5, 10, and 27%. CONCLUSION: The size of nonpalpable breast cancers measured on the excised gross specimen and by mammogram accurately predicts the likelihood of axillary node metastasis.

Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer.

PURPOSE: Considerable attention has been focused on the chemopreventive properties of fenretinide against carcinogen-induced rodent mammary cancer. Less is known about its direct antitumor effects. The combination of tamoxifen and fenretinide is more effective than tamoxifen or fenretinide alone in prevention of rat mammary cancer. However, the combined toxicity of tamoxifen plus fenretinide in humans is unknown. Therefore, we performed a phase I/II trial in women with estrogen receptor (ER)-positive or progesterone receptor (PR)-positive, previously untreated metastatic breast cancer. PATIENTS AND METHODS: Groups of three patients received tamoxifen 20 mg/d, or tamoxifen plus fenretinide 100, 200, 300, or 400 mg/d. Patients who received fenretinide enjoyed a 3-day "drug holiday" every 4 weeks. Serum levels of fenretinide and its major metabolites were monitored. Patients were monitored for known toxicities of tamoxifen and vitamin A analogs, as well as for response. RESULTS: There were no significant adverse effects on renal, hepatic, hematologic, or lipid values. Nyctalopia, photophobia, cheilitis, and pruritus were not observed. Improvement or stabilization of disease occurred in 12 of 15 patients. CONCLUSION: We conclude that tamoxifen administered with fenretinide is nontoxic. Phase III trials of tamoxifen versus tamoxifen plus fenretinide are warranted.

Percutaneous interstitial laser therapy of a patient with recurrent hepatoma in a transplanted liver.

We report in situ treatment, by focal hyperthermia, of a recurrent hepatoma in the transplanted liver of a 53-year-old man. Hyperthermia was generated by neodymium-yttrium-aluminum-garnet laser, which was delivered through a fiber placed inside a 19-gauge needle and inserted percutaneously into the liver under ultrasound guidance. The effect was monitored in real time by ultrasound and subsequently confirmed by computerized tomography and needle core biopsy. Objectively the tumor growth was halted for 3 months, indicating partial response to this minimally invasive treatment.

Histologic evaluation of rat mammary tumor necrosis by interstitial Nd:YAG laser hyperthermia.

The extent of coagulative necrosis caused by interstitial laser hyperthermia was measured for different quantities of laser energy in a rat mammary tumor model. Continuous wave Nd:YAG laser at a power level of 5 W was focused onto a 600 mu diameter bare tip quartz fiber and placed inside a 19-gauge needle, which allowed the para-axial flow of normal saline at 1 cc/min. A microthermocouple soldered to the outside of the probe continuously provided the interstitial temperature. After the probe was inserted into the tumor, it was withdrawn as laser energy was administered at a rate sufficient to maintain the temperature within 42-45 degrees C. Tumors were excised after 48 hours, fixed in formalin, cut in 3 mm slices, and the coagulated surfaces measured microscopically. Laser fiber transmission loss was 1% per 1,000 J of laser energy and the average time required to coagulate 1 cc of tumor was 2 minutes. There was a statistically significant correlation between the volume of tumor necrosis and the level of laser irradiation (r = 0.71, P less than 0.001). It is concluded that the described technique is an efficient method of tumor coagulation by interstitial laser hyperthermia and proportionally larger volumes of necrosis are created with greater amounts of laser energy.

Nonpalpable breast lesions: findings of stereotaxic needle-core biopsy and fine-needle aspiration cytology.

Two hundred fifty mammographically detected nonpalpable breast lesions suspicious for malignancy in women who underwent routine screening mammography were stereotaxically localized. Fine-needle-aspiration (FNA) cytologic specimens and needle-core biopsy specimens were obtained before open biopsy in every case. Seventy-six lesions (30.4%) were malignant. Sixty-three (83%) of these 76 cancers were 1 cm long or smaller. Needle-core biopsy alone was used to diagnose conclusively 41% (n = 31) of these cancers, while FNA cytologic study alone was used to diagnose 32% (n = 24). No false-positive results occurred with either test. The same diagnosis was reached in 54% (n = 41) when the combined results of both needle tests were considered. In applying the two needle tests to 125 mammographically defined low-suspicion lesions, 85 (68%) were found to be benign by means of either one or both needle tests; there was one lobular carcinoma in situ. By applying this algorithm, 85 (34%) of 250 patients with abnormal mammograms, or one-third of all patients recommended for open biopsy, might have avoided surgery.

A prospective study of double diagnosis of nonpalpable lesions of the breast.

Approximately three-fourths of open biopsies of the breast performed for mammographically detected suspicious lesions are shown histologically to be benign. Under the narrow conditions described herein, stereotaxic fine-needle aspiration (FNA) can identify these lesions with an accuracy of more than 90 per cent and a false-negative rate of 5 per cent. In an effort to reduce this failure rate, the mammographic appearance and stereotaxic FNA results of these lesions each were given scores on a scale of zero (benign) to five (malignant), to derive an over-all risk score prospectively applied to 264 suspicious occult lesions of the breast prior to open, biopsy. While all 264 lesions could be assigned a mammographic score, adequate tissue for assignment of a cytologic score could be obtained from 150 lesions. Of the 150 evaluable lesions, 53 were malignant and 97 were benign, historically. With a total score of two as the threshold for open biopsy, 21 of 150 (14 per cent) were proved to be benign, with no false-negative findings. If the total threshold score mandating an open biopsy was raised to four, the comparable figures were 61 of 150 (40 per cent) benign lesions and two false-negative instances of carcinoma in situ. Provided adequate tissue is aspirated for cytologic examination, we conclude that this algorithm has practical value in the management of nonpalpable lesions of the breast in that it can reliably identify a fraction of the benign lesions and spare these patients an operation.

Protection of fiber function by para-axial fluid flow in interstitial laser therapy of malignant tumors.

In the past, interstitial laser therapy frequently has failed because of the damage to the bare fiber tip due to intense heat generated at the point of contact. Using a rat mammary tumor model, we describe a method of placing a 600 micron fiber inside a gauge 19 needle cannula after its insertion into the tumor. With this device continuous wave Nd:YAG laser is delivered to the target tumor while 0.9% saline flows para-axially into the tumor. Significant coagulation necrosis was induced with 500 joules at 5 watts, 100 seconds and 1 cc per minute of saline while the needle-fiber is pulled out of the tumor by 10 mm. The mean transmission loss after 500 joules was 2% in ten experiments. The tumor edema due to 1.5 ml of saline was transient. We conclude that successful hyperthermic coagulation necrosis by Nd:YAG laser can be achieved with minimal transmission loss by employing the above technique.