Extensive Intraductal Component Research Articles

The influence of age and extensive intraductal component histology upon breast lumpectomy margin assessment as a predictor of residual tumor

Purpose: Young age and extensive intraductal component (EIC) histology have been shown to be associated with increased local recurrence in women treated with breast conservation therapy. This study was conducted to determine if the status of the lumpectomy specimen margin consistently predicted for residual tumor burden risk irrespective of these variables. Methods and Materials: As part of an institutional prospective approach for breast conservation therapy (BCT), 265 cases with AJCC Stage I/II carcinoma with an initial excision margin that was ≤2 mm or indeterminate were subjected to reexcision. The probability of residual tumor (+RE) was evaluated with respect to tumor size, histopathologic subtype (invasive ductal carcinoma, invasive ductal carcinoma with an EIC, and invasive lobular carcinoma), relative closeness of the measured margin, and the extent of margin positivity graded as focal, minimal, moderate, or extensive. The amount of residual tumor was graded as microscopic, small, medium, or large. All variables were analyzed for patient age ≤45 or >45 years. Results: There was no significant difference in the incidence of a +RE according to age ≤45 versus >45 years when the margin was >0 ≤2 mm. Of the patients aged ≤45 years, the incidence of a +RE with a margin that was positive as compared to >0 ≤2 mm was 71% vs. 23%, respectively ( p = 0.002). For women >45 years old, the difference in the incidence of +RE comparing margins that were positive or >0 ≤2 mm was not significant at 50% vs. 40%, respectively ( p = 0.23). For all cases in aggregate, age ≤45 years was associated with a greater incidence of +RE as compared to patients aged >45 years with the discrepant incidence of a +RE by age strata most pronounced for focally positive margins (60% vs. 18%; p ≤ 0.05). In a logistic regression analysis, age (per year, as a continuous variable) and an EIC histology were significantly associated with the probability of a +RE (odds ratio [OR] = 0.80, p = 0.05 and OR = 1.9, p = 0.01, respectively). Tumor size was not significant ( p = 0.23). In patients with an EIC histology, margin status is generally less predictive for differences in the incidence of a +RE. Further, the overall magnitude of difference in the incidence of a +RE related to age appears to be minimized when an EIC histology is present. In contrast, for cases classified as having non-EIC histology, there is a near-linear relationship for both age strata with respect to margin status and the incidence of a +RE. When histology is classified as non-EIC, age ≤45 years is consistently associated with a greater risk of residual tumor for all margin status categories. When the extent of margin positivity was graded as focal or minimal, residual tumor was semiquantitatively estimated as a medium/large amount in 33% versus 26% of cases aged ≤45 or >45 years, respectively ( p = 0.62). Conclusion: For positive lumpectomy specimen margins, younger age is associated with an increased residual tumor risk. An EIC histology appears to be associated with an elevated risk of residual tumor irrespective of age and may undermine the predictive utility of margin status. Therefore, age and an EIC histology should be factored into risk assessments for residual tumor that rely upon margin assessment.

The unsatisfactory margin in breast cancer surgery

Background: Surgical margin involvement with breast cancer usually results in obligatory reexcision or mastectomy. While unalterable occult host and pathologic factors may interfere with margin clearance during the initial excision, it is possible that alterations in surgical technique might increase the likelihood of obtaining satisfactory margins. Methods: Two hundred and thirty-five patients who were candidates for breast conservation therapy were identified for 1991 and 1996 using the Tumor Registry. Margins were defined as “unsatisfactory” if there was microscopic involvement with tumor or the margin was close at initial excisional biopsy and the surgeon opted for reexcision. Multiple logistic regression analyses of factors associated with margin status were performed. Results: One hundred thirty-two (56%) patients had positive or close (unsatisfactory) margins; this rate increased from 51% in 1991 to 59% in 1996. Patients with unsatisfactory margins underwent more procedures (mean 2.0 versus 1.2; P <0.0001) than patients whose margins were satisfactory. The breast conservation rate for patients with unsatisfactory margins was 64% compared with 99% for patients with satisfactory margins. A multiple logistic regression demonstrated that patients with unsatisfactory margins were 67 times more likely to have a mastectomy than patients whose margins were satisfactory after adjusting for other significant factors ( P <0.0001). The practice of fine needle aspiration biopsy, orientation of specimen margins by the surgeon, and reexcision of tumor at the first operation were statistically significant technical factors in obtaining satisfactory margins. Significant pathology factors were extensive intraductal component (EIC), lobular or ductal extension, and tumor size. Conclusion: These data show that technical factors in the surgical management of breast cancer, as well as biological factors such as EIC, can influence the success of breast conservation.

Margin assessment by cavity shaving after breast-conserving surgery: analysis and follow-up of 543 patients

Aims To analyse cavity shaving as a method of assessing completeness of surgical excision after breast-conserving surgery. Methods Shavings were taken from the wall of the cavity remaining in the breast after breast-conserving surgery in 543 women. Each shaving was extensively sectioned and the presence and type of microscopic disease recorded. Disease in cavity shavings (tumour bed positivity) was correlated with clinicopathological factors as well as overall survival. Results Tumour bed positivity (TBP) was found in 37% of patients (16% with invasive disease). Patients were selected for further surgery according to the extent of positivity, which varied widely. A total of 15% of patients underwent re-excision or mastectomy. TBP was significantly associated with high tumour grade, presence of an extensive intraduct component, young age and large tumour diameter. It was also associated with a significantly shorter overall survival when compared to patients who were tumour bed negative. Conclusions Cavity shaving is a practical and sensitive method of assessing completeness of excision after breast-conserving surgery. In addition it may provide useful prognostic information.

Apoptosis in breast cancer and its relationship to clinicopathological characteristics and prognosis

Background and Objectives Apoptosis is essential to maintain homeostasis in living organisms and occurs in a variety of tissues in response to both physiological and pathological stimuli. In breast cancer, most cytotoxic drugs and hormonal treatments induce apoptosis. We studied the relationships between apoptosis and clinicopathological variables or prognosis in 143 patients with operable breast cancer. Methods Apoptosis was numerically graded in 5 consecutive 40× high-power fields (HPF) of hematoxylin-eosin (H&E) stained sections, since we showed that there was a significant correlation of H&E staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Results The average number of apoptotic cells was 19.9 (0∼168)/5 HPF, and cases were classified into 3 groups based on the number of apoptotic cells/5HPF: 0 to 10, 11 to 30, and 31+. The level of apoptosis increased with increasing size of the tumor, and apoptosis was rarely seen in tumors with positive ER or lower proliferative activity, as assessed by DNA polymerase α. As shown by DNA content analysis, apoptotic cells were observed more frequently in tumors with low G1 and high S-phase fractions. In addition, apoptosis was correlated with overexpression of p53 and poor prognosis. Although apoptosis did not correlate with EIC (extensive intraductal component) status, tumors with comedo component had higher values of apoptosis than those without comedo component. Conclusions In breast cancer, apoptosis might reflect biological behavior, namely a higher degree of biological aggressiveness and unfavorable prognosis. J. Surg. Oncol. 1999;71:226–234. © 1999 Wiley-Liss, Inc.

High-dose-rate brachytherapy for early breast cancer: an ambulatory technique

Purpose: To evaluate tolerance and efficiency of a boost dose delivered by high-dose-rate brachytherapy (HDRB) in conservative treatment of breast cancer. To evaluate the feasibility of brachytherapy on an out-patient basis. Methods: One hundred and six patients with T1–T2, N0–N1 breast cancers (108 breasts) have been treated with lumpectomy, external irradiation (45 Gy in 5 weeks), and a boost dose on the tumor bed with HDR iridium brachytherapy. Two fractions of 5 Gy were delivered 6 or 24 hours apart. Implantation was done during the lumpectomy (group A: 24 cases) or 3 to 4 weeks after the end of external irradiation (group B: 84 cases). For group B, the application was performed on local anesthesia, and did not require hospitalization. Characteristics of the population were as follows: T1: 77 (71.3%); T2: 31 (28.7%); median tumor size: 1.5 cm; histology: intraductal carcinomas (DCIS): 14 (13%); infiltrative ductal carcinomas (IDC): 84 (77.8%); others: 10 (9.2%). For IDC, surgical margins were found positive in 15 cases, and an extensive intraductal component was present in 22 cases. Results: All ambulatory HDR implants were performed as planned. No immediate toxicity was noticed, except 5 local hematomas. With a median follow-up of 45 months, 5 local relapses were observed (5-year local relapse rate: 5.1%). Only histological grade III was significantly correlated with local relapse. The 5-year disease-free survival and overall survival were respectively 93.8% and 93.3%. Cosmetic result was evaluated in 87 cases, and was good or excellent in 48 cases (63.2%), acceptable in 27 cases, and poor in 5 cases. Conclusion: HDRB allows the boost dose to be performed on an out-patient basis. It seems to offer the same local control as other boost techniques for localized breast cancer with acceptable cosmetic results.

Apoptosis in breast cancer and its relationship to clinicopathological characteristics and prognosis.

Apoptosis is essential to maintain homeostasis in living organisms and occurs in a variety of tissues in response to both physiological and pathological stimuli. In breast cancer, most cytotoxic drugs and hormonal treatments induce apoptosis. We studied the relationships between apoptosis and clinicopathological variables or prognosis in 143 patients with operable breast cancer. Apoptosis was numerically graded in 5 consecutive 40x high-power fields (HPF) of hematoxylin-eosin (H&E) stained sections, since we showed that there was a significant correlation of H&E staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The average number of apoptotic cells was 19.9 (0 approximately 168)/5 HPF, and cases were classified into 3 groups based on the number of apoptotic cells/5HPF: 0 to 10, 11 to 30, and 31+. The level of apoptosis increased with increasing size of the tumor, and apoptosis was rarely seen in tumors with positive ER or lower proliferative activity, as assessed by DNA polymerase alpha. As shown by DNA content analysis, apoptotic cells were observed more frequently in tumors with low G1 and high S-phase fractions. In addition, apoptosis was correlated with overexpression of p53 and poor prognosis. Although apoptosis did not correlate with EIC (extensive intraductal component) status, tumors with comedo component had higher values of apoptosis than those without comedo component. In breast cancer, apoptosis might reflect biological behavior, namely a higher degree of biological aggressiveness and unfavorable prognosis.

Malignant Seeding of the Lumpectomy Cavity upon Breast-Conserving Surgery

One of the etiologic factors involved in local recurrence after breast-conserving surgery may be malignant seeding of the wound during the lumpectomy procedure. A total of 340 patients with stage I and II breast cancer were entered into the study. Of these, 270 patients received breast-conserving surgery (BCS group), and the other 70 patients underwent mastectomy (control group). After resection, lavage cytology was performed at the surgical wound. There were 55 patients (20.4%) who showed positive lavage cytology in the BCS group. In the control group, there were only 3 patients (4.3%) with positive cytology. Positivity was significantly higher in the former group (p = 0.00064). Patients with evidence of cutting across cancer lesions showed significantly higher positive rates in lavage cytology (p < 0.00001). Positivity in lavage cytology was significantly higher in patients with positive surgical margins evaluated by frozen sections (p = 0.0017), touch cytology (p < 0.0001) and formalin-fixed, paraffin-embedded sections (lateral or medial margin; p = 0.0036, anterior and posterior margin: p = 0.0210). The positivity was also significantly higher in patients with an extensive intraductal component (p < 0.0001), and less than or equal to 50 (p = 0.0061) years of age. Multivariate analysis revealed that the highest relative risk factor for positive cytology was evidence of cutting across cancer lesions (relative risk = 8.166; p < 0.00001).

The relationship between findings on pre-treatment mammograms and local recurrence after breast-conserving therapy for invasive breast cancer

AimsThis study was planned (a) to determine the correlation between findings on the pre-treatment mammogram and local recurrence after breast-conserving therapy (BCT), and (b) to analyse the relationship between mammographical features, specific pathological characteristics and the need for re-excision.MethodThe size and outline of the lesion, the presence of suspect microcalcifications and signs of multifocality on pre-treatment mammograms of 39 patients with local recurrence after BCT and 126 randomly selected control patients without local recurrence were compared. Tissue slides of the primary tumour were reviewed to confirm the histological type and grade, the aspect of the margins, microscopic margin involvement, presence of vascular invasion and the presence and extent of an intraductal component.ResultsAmong patients ≤50 years of age, the proportion with a mammographically occult tumour was 48% of the patients with local recurrence and 26% of the control group (P=0.05). In the age group ≥50 years, 67% of the patients with local recurrence had a non-circumscribed lesion compared to 9% of the control group (P<0.001). Suspect microcalcifications on the mammogram were associated with the finding of an extensive intraductal component, vascular invasion and a higher histological grade by the pathologist. Patients with a non-circumscribed density or a scirrhous lesion needed re-excision more often (30 and 33%, respectively) than those with a well-circumscribed density (9%).ConclusionsAlthough the number of patients was small, this study indicates that some mammographical features are associated with a higher risk of local recurrence after BCT and the need for re-excision. This was supported by the findings of the pathological review.

Indications and contraindications for breast preservation in patients with breast cancer

Roughly 70% of all patients with breast cancer can be treated by breast-preserving procedures under optimal circumstances. Risk factors for the development of local recurrences are age, angioinvasion, poor differentiation of the tumor, negative steroid hormone receptors, extensive intraductal component and positive margins. Contraindications for breast preservation are large tumors without remission after preoperative chemotherapy, multicentricity, extensive intraductal component, large ductal carcinoma in situ, inflammatory breast cancer after preoperative chemotherapy, Paget disease and local recurrence after breast-conserving surgery. Preoperative needle biopsy allows determination of nearly all of the risk factors. To further increase the rate of breast conservation, preoperative chemotherapy should be used more extensively.

Three-dimensional breast biopsy and surgery

For the histological verification of suspicious non-palpable small breast tumors, the three-dimensional breast biopsy applied as cylindrical extirpation using the ABBI system is the optimal solution at present. Because of the possibility of performing mammography during the operation, errors of localization can be corrected and incorrect incisions avoided. Taking the three radiomorphologically leading symptoms into consideration--suspicious microcalcification, focal shadow and structural irregularity--it can be stated that the digital mammography of the ABBI system is more sensitive than the conventional one for detecting microcalcification, but focal shadow and structural irregularity are detected less well by digital technique. These structures should be preoperatively marked by using sonography. After the complete removal of suspicious microcalcification checked by digital mammography during the operation, residual tumor might be found in a second excision when histologically invasive or intraductal tumor terminations reach the excision margin (R1 resection). Thirteen invasive and 8 intraductal carcinomas were found in 80 cases of cylindrical extirpation using the ABBI system. In 7 procedures carried out to exclude an in-breast recurrence, 3 intraductal carcinomas and 1 invasive carcinoma were observed. In 8 of 12 invasive carcinomas and in 1 of 5 intraductal carcinomas, breast-conserving therapy was indicated. Two cases of invasive carcinoma fulfilled the criteria applied (minimal tumor-free margin > 2 mm, no extensive intraductal component) to use the ABBI cylinder as lumpectomy without a second excision to follow.

Irradiation of the tumor bed alone after lumpectomy in selected patients with early-stage breast cancer treated with breast conserving therapy.

We present the interim findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast conserving therapy (BCT). From 1 March 1993 through 1 January 1995, 50 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation alone using an interstitial LDR implant. Patients were eligible if their tumor was an infiltrating ductal carcinoma < or =3 cm in diameter, surgical margins were clear by at least 2 mm, the tumor did not contain an extensive intraductal component, the axilla was surgically staged with < or =3 nodes involved with cancer, and a postoperative mammogram was performed. Implants were positioned using a template guide delivering 50 Gy over 96 hr to the lumpectomy bed plus a 1-2-cm margin. Local control, cosmetic outcome, and complications were assessed. Patients ranged in age from 40 to 84 years (median, 65). The median tumor size was 10 mm (range, 1-25). Seventeen of 50 patients (34%) had well-differentiated tumors, 22 (44%) had moderately differentiated tumors, and in 11 (22%) the tumor was poorly differentiated. Forty-five patients (90%) were node-negative while five (10%) had 1-3 positive nodes. A total of 23 (46%) patients were placed on tamoxifen and 3 (6%) received adjuvant systemic chemotherapy. No patient was lost to follow-up. The median follow-up for surviving patients is 47 months (range, 37-59). No patient has experienced a local, regional, or distant failure. Three patients have died at 19, 33, and 39 months after treatment. All were without clinical evidence of recurrent disease and all deaths were unrelated to treatment. Good-to-excellent cosmetic results have been observed in 49 of 50 patients (98%) (median cosmetic follow-up was 44 months with a range of 19-59). No patient has experienced significant sequelae related to their implant. Interim results with treatment of the tumor bed alone with an LDR interstitial implant appear promising. Long-term follow-up of these patients and additional studies will be necessary to establish the equivalence of this treatment approach compared to standard BCT.

ANALYSIS OF 28 CASES WITH POSITIVE SURGICAL MARGINS IN BREAST-CONSERVING TREATMENT FOR BREAST CANCER

A retrospective review was made of 137 patients tried the breast-conserving treatment (BCT) at the Osaka Teishin Hospital since Junuary 1990 until May 1997. BCT consisted of quadrantectomy with axillary dissection. To assure complete resection of the breast cancer, we histopathologically examined three margins of the residual breast during operation. In case of a positive margin finding, mastectomy or total glandectomy was performed. One-hundred nine patients (79.6%) were successfully treated with BCT _??_group A_??_, whereas 28 patients (20.4%) required a modification of BCT in order to gain negative surgical margins _??_group B_??_. Surgical positive margins were mainly due to extensive intraductal components (EIC). We compared the two groups in regards to their clinico-pathological futures. The patients in group B were more likely to have factors such as younger age (p<0.05), premenopousal (p<0.05), positive estrogen receptor (ER)/progesterone receptor (PgR) (p<0.05), DNA index=1.00 (p<0.05) and pathologically involved lymph nodes (p<0.05). Mastopathic change and/or atypical ductal hyperplasia (ADH) were more frequently observed surrounding the cancerous lesions of group B than of group A (p<0.0001). There were no clinical factors that characterized the extensive intraductal component before the operation. Therefore, the rapid intraoperative pathological consultation for surgical margins and the strict patho-logical examination of the resected specimen are very important and useful in order to guarantee cancer-free surgical margins in BCT.

Lymph node metastasis in breast cancer: common prognostic markers lack predictive value.

The purpose of this study was to determine whether routine biologic tumor markers can predict lymph node status. The authors attempted to discover whether predictors of axillary lymph node metastasis based on biologic characteristic of primary breast cancers exist. Eight hundred and fifty-one patients with invasive breast cancer who underwent surgical treatment, including axillary lymph node dissection, at a tertiary referral center were studied. Univariate and multivariate analysis were performed on prospectively gathered data from a breast cancer registry, including pathology, site of primary lesion in the breast, estrogen and progesterone receptor status, DNA index, S-phase fraction, nuclear grade, and extensive intraductal component. Outcome was determined by (1) the presence of any lymph node metastasis and (2) the presence of 10 or more lymph node metastases. The only independent predictors of lymph node metastasis were primary tumor size and pathology. For predicting 10 or more metastases, only size and ER-negative status were independent predictors. These factors accounted for less than 20% of the regression, implying that more than 80% of lymph node metastases are not explained by the regression model. Lymph node metastases were seen in 8.3% of T1a, 15.3% of T1b, and 30.7% of T1c lesions. Biologic tumor markers are not reliable predictors of lymph node metastasis, except possibly for T1a lesions, therefore direct pathologic evaluation of lymph node status cannot be abandoned. Efforts to determine lymph node status through other methods such as sentinel lymph node biopsy are warranted.

Radiation therapy without boost for breast conserving surgery patients with positive surgical margin or extensive intraductal component

Radiation therapy without boost for breast conserving surgery patients with positive surgical margin or extensive intraductal component

The presence of proliferative breast disease with atypia does not significantly influence outcome in early-stage invasive breast cancer treated with conservative surgery and radiation

Purpose: To evaluate the influence of the benign background breast-tissue change of atypical hyperplasia (AH) on outcome in patients with early-stage invasive breast cancer treated with conservative surgery and radiation. Materials and Methods: Four hundred and sixty women with Stage I—II breast cancer treated with conservative surgery and radiation from 1982–1994 had pathologic assessment of their background adjacent benign breast tissue. The median follow-up was 5.6 years (range 0.1–15). The median age was 55 years (range 24–88). Of these, 23% had positive axillary nodes; 25% received adjuvant chemotherapy (CMF or CAF) with (9%) or without (17%) tamoxifen. Of the total, 24% received adjuvant tamoxifen alone. The patients were divided into 2 groups: 131 patients with atypical hyperplasia (ductal, 99 patients; lobular, 20 pts; and type not specified, 12 pts), and 329 patients with no proliferative changes or proliferative changes without atypia. Result: A statistically significant difference was observed between the 2 groups for method of detection, primary tumor size, presence of lobular carcinoma in situ (LCIS), pathologic nodal status, region(s) treated with radiation, and type of adjuvant therapy. Patients with atypical hyperplasia (AH) had smaller primary tumors (T1 80% vs. 70%) more often detected solely by mammography (51% vs. 36%) with negative axillary nodes (87% vs. 73%) and radiation treatment to the breast only (93% vs. 78%). LCIS was observed in 9% of the patients with AH and 3% of those without AH. Patients with AH more often received tamoxifen alone (32% vs. 21%), rather than chemotherapy (15% vs. 29%). There were no statistically significant differences between the 2 groups for race, age, menopausal status, family history, histology, histologic subtype DCIS when present, the presence or absence of an extensive intraductal component, final margin status, estrogen or progesterone receptor status, use of re-excision, or total radiation dose to the primary. The 5- and 10-year actuarial ipsilateral breast tumor recurrence rates were 2% and 12% for patients with AH and 4% and 8% for those without AH ( p = 0.44). Younger women or those with a positive family history of breast cancer with AH did not have an increased rate of breast failure when compared to similar patients without AH. There were no significant differences in the 5- and 10-year actuarial rates of distant metastases (AH 5- and 10-year 7% and 7%, no AH 5- and 10-year 8% and 16%, p = 0.31), regional node recurrence (AH 1% and 1%, no AH 1% and 1%, p = 0.71), contralateral breast cancer (AH 3% and 3%, no AH 3% and 8%, p = 0.71), overall survival (AH 95% and 86%, no AH 95% and 89%, p = 0.79), or cause-specific survival (AH 98% and 95%, no AH 96% and 91%, p = 0.27). Subset analysis for ipsilateral breast tumor recurrence, distant metastases, overall, and cause-specific survival for T1 vs. T2 tumors and path node-negative vs. path node-positive patients revealed no significant differences between the 2 groups. Conclusion: AH was not associated with an increased risk of ipsilateral breast tumor recurrence or contralateral breast cancer in this study of patients with invasive breast cancer treated with conservative surgery and radiation. Therefore, the presence of proliferative changes with atypia in background benign breast tissue should not be a contraindication to breast-conservation therapy.

Prognostic value of cathepsin D expression and association with histomorphological subtypes in breast cancer.

This study investigated the prognostic value of immunohistochemically detected cathepsin D expression in 103 invasive ductal carcinomas of the breast at stages pT1 and 2. We also assessed the association between cathepsin D expression and histomorphological tumour subtypes (invasive ductal carcinoma with extensive intraductal component, multifocal tumour). Cathepsin D expression was examined at two cut-off levels (positive and highly positive) and separately identified within the epithelial and stromal component of all tumours. Positive and highly positive epithelial expression was detected in 32 (31.1%) and 20 (19.4%) patients respectively. Stromal expression was found in 35 (34%) and 19 (18.4%) cases respectively. Epithelial cathepsin D expression was associated with stage and nuclear grade, but not with lymph node or oestrogen receptor status. Positive and highly positive epithelial cathepsin D expression showed significant prognostic value for overall survival (P = 0.003 and 0.01) and recurrence-free interval (P = 0.04 and 0.02). Cathepsin D expression in stromal cells was not associated with either several established prognostic factors or survival. Multivariate analysis revealed that cathepsin D expression failed to be an independent predictor of patients' outcome. Cathepsin D expression shows no significant association with histomorphological subtypes of breast cancer. Our study supports the prognostic impact of immunohistochemically detected cathepsin D expression in the epithelial component of breast cancer.

Biological Effects of Heavy Ion Beam on Human Breast Cancers.

BACKGROUND: Radioresistance of the extensive intraductal component (EIC) is amajor limiting factor in breast conserving therapy (BCT). The purpose of the present experiment was to elucidate the biological effects of a carbon beam on human breast cancer cell lines in order to evaluate its clinical benefits in BCT. METHODS: Human breast cancer cell lines, both grown in culture and inoculated into nude mice were subjected to X-ray (200 kV) and heavy ion beam (290 MeV/u carbon beam) irradiation. The relative biological effectiveness (RBE) of the carbon beam and X-ray irradiation was determined at the level of D10 (10% survival dose) on the dose-survival curve. By using a colony forming assay the survival curves of the three cultured cell lines (YMB-I, OUUB-M, CRL-1500) at a linear energy transfer (LET) of 80 keV/µ m were obtained. Cancer established in nude mice was exposed to single-dose and triple-fractionated irradiation at a LET of 50 keV/µm. The growth of tumorsat various doses was observed and the survival curves were determined using thetumor regrowth assay. RESULTS: The RBE of the carbon beam on each cell line ranged from 2.17 to 2.89 (2.59+/-0.37). That of the tumor in nude mice was 1.53 and 2.00 on exposure to single-dose and fractionated irradiation, respectively. CONCLUSION: Human breast cancer cell lines showed high intrinsic sensitivity to a carbon beam and its effects on the tumor were enhanced by fractionated irradiation. It is worthy using carbon beam is applied to use for clinical trials inBCT.

Extensive intraductal component (EIC) and estrogen receptor (ER) status in breast cancer.

The extensive intraductal component (EIC) of primary breast carcinoma is a special spread pattern observed in the breast. Extensive intraductal component may extend diffusely over the entire breast. Therefore, EIC is considered to be an important risk factor for local recurrence in breast-conserving therapy. However, the pathogenesis of EIC remains uncertain. Whether or not the estrogen receptor (ER) has an influence on its biologic behavior has not been fully studied. A consecutive series of 142 breast carcinomas submitted to the pathology department were examined on step gross sections of 5.0 mm thick. Extensive intraductal component was determined and divided into three types. Estrogen receptor was examined using both immunohistochemistry (ER-IHC) and enzyme immunoassay (ER-EIA). Extensive intraductal component was found in 78 of 138 (56.52%) invasive carcinomas including invasive ductal carcinoma with a predominant intraductal component. Estrogen receptor-IHC positivity was 42.96% (61/142) in the invasive breast carcinoma. Estrogen receptor positivity showed no significant difference between EIC-positive and -negative cases, as well as between EIC and invasive main tumor in the EIC-positive cases. But within the EIC-positive group, ER positivity was found to be higher in the peripheral type of EIC-II and EIC-III than in the central type of EIC-I (P < 0.05). Although ER may not play an essential role in the pathogenesis of EIC, it has shown some significance in the development of peripheral type EIC because of its higher presence in the peripheral type of EIC-II and EIC-III than in the central type of EIC-I.

Local Recurrence after Conservative Surgery without Postoperative Radiation for Pure Tubular Carcinoma of the Breast:A Case Report with Reference to Multifocality of Tubular Carcinoma.

A 49-year-old premenopausal woman with stage I breast carcinoma underwent left quadrantectomy with axillary dissection in 1992. The tumor was 0.7x0.5 cm Histopathologically, this was a pure tubular carcinoma without lymph node metastasis or lymphatic or vascular invasion. Although the surgical margin was pathologically negative, atypical ductal hyperplasia was present close to the cut margin's edge. Neither adjuvant chemotherapy nor radiotherapy had been given after the operation. Approximately 5 years after the first surgery, she had a local recurrence in the vicinity of the operative wound. There was no clinical evidence of distant metastasis. A salvage mastectomy was performed. Histopathological examination revealed that the second tumor was an invasive ductal carcinoma, histological grade 2, with extensive intraductal component. It was difficult to determine whether this was a true in-breast recurrence or a second primary cancer. Overexpression of p53 and c-erbB-2 was observed in the second tumor. Estrogen receptor and progesterone receptor were both negative. No postoperative chemotherapy was given. Multifocality and atypical ductal hyperplasia were observed in 7(87.5%)and 6(75%) of 8 patients, respectively, with tubular carcinoma between 1991and 1997 at the National Cancer Center Hospital. Coexisting disease associated with tubular carcinoma suggests that radiotherapy may be an important component of breast conservation treatment to prevent local recurrence in this type of tumor.

Rapid intraoperative scrape cytology assessment of surgical margins in breast conservation surgery

Rapid intraoperative scrape cytologic examination for diagnosing surgical margin involvement of specimens obtained by breast conservation surgery was evaluated. Four surgical margins(nipple side, two lateral sides and distal side)of the removed breast tissue were cytologically examined and histologically compared following segmentectomy in 50 breast cancer patients(200 margins). Intraductal carcinoma had a tendency to spread most extensively to the nipple, compared with other margins. The margin positive rate of tumors with ductal spread(DS)of over 20mm was significantly higher than in tumors with a DS under 20 mm(52.2% vs 7.4%)(P < 0.001). of 50 canditates 10 patients underwent total mastectomy due to positive margins on repeat cytologic examination after re-excision. Four of the 10 patients had an extensive intraductal component on microscopy. The sensitivity, specificity and accuracy of cytology were 96.4 %, 90.7% and 91.5%, respectively.Scrape cytology is useful to determine surgical margin involvement after segmentectomy for breast cancer, although overestimation of involvement will tend to result.