Notizen: Abstract: The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30–13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p 〈 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were ≤2 cm in size (RR = 13.68, 95% CI 1.06–175.76), whereas no such association was observed among patients with HER-2-positive tumors larger than 2 cm. Eligible patients without available tumor tissue tended to have smaller tumors compared to study participants. Our results might partly explain the variation in evidence across HER-2 prognostic studies using fixed tissue and might apply to other putative markers of prognosis in breast cancer. 

Notizen: ▪ Abstract: Occult primary breast carcinoma presenting as isolated ipsilateral axillary lymph node metastases in patients with normal mammograms and normal physical exams accounts for less than 1% of all breast carcinomas. Contrast-enhanced magnetic resonance imaging (MRI) may identify the site of primary breast carcinoma and effect management of these patients. We report on eight consecutive women evaluated in our multidisciplinary clinic who had biopsy-proven metastatic adenocarcinomas to axillary lymph nodes and occult primary carcinomas. Each patient underwent MRI at 1.5 T with a volumetric fast-spoiled gradient-echo (3D FSPGR) pulse sequence before and after injection of gadopentetate dimeglumine. Wire localization of suspicious areas of enhancement was performed under MRI or mammography guidance followed by surgical excision. Seven (88%) of the eight normal mammograms showed dense (〉50%) breast parenchyma. In two (25%) of the eight patients, suspicious focal or regional enhancement was seen on MRI. Following wire localization and excision, pathologic exam showed an invasive ductal carcinoma and ductal carcinoma in situ with invasion corresponding to the MRI enhancement in the two cases. Breast MRI can identify the primary tumor site and influence management of patients presenting with clinically and mammographically occult primary breast carcinomas. ▪

Notizen: Abstract Background: The finding of lobular carcinoma in situ (LCIS) in the breast has generally prompted treatment with unilateral or bilateral mastectomy. Most experts now feel that LCIS simply identifies a woman who is at high risk to develop future breast cancer and requires only close clinical and mammographic follow-up. This approach has been recommended at our institution for 〉15 years. This study defines the natural history of a population of women with LCIS who were treated by observation alone. Methods: Women with a pathologic diagnosis of LCIS were identified by tumor registry search. Records and pathology were reviewed. Radiographic-pathologic correlation was performed on women who had undergone mammographic-localized breast biopsies. One hundred forty-nine women with LCIS were identified. Eighty four were excluded from analysis because of synchronous invasive cancer or ductal carcinoma in situ (DCIS). The remaining 65 women formed the basis of this report. Results: Sixty-five women with LCIS were treated from 1963 through 1990. Median follow-up was 83 months. No women were lost to follow-up. Median age at diagnosis was 48 years (range 37–81), and 32% had a family history of breast cancer. Clinical findings leading to biopsy were breast mass in 43, nipple discharge in three, and mammographic abnormality in 19. Mammographic-pathologic correlation showed that the focus of LCIS in these 19 women was not associated with the mammographic abnormality. Fourteen of 65 women underwent mastectomy after diagnosis of LCIS (nine ipsilateral, five bilateral). Fifty-one of 65 women elected observation alone. In the observation group, 13 of 51 women (25%) underwent a second breast biopsy for a clinical or mammographic abnormality during the follow-up period. The median interval to biopsy was 50 months. Pathology was benign in two, LCIS in seven, DCIS in one, and invasive cancer in three. All seven women with LCIS on subsequent biopsy continued with observation and none developed breast cancer. All four cancers were detected by mammography without an associated palpable mass. Three of four cancer masses were 〈1 cm in diameter. The woman with DCIS was 47 years of age and developed DCIS 106 months after LCIS diagnosis. She was treated by total mastectomy and is disease free 108 months later. The three women with invasive cancer developed this at 41, 53, and 69 months after diagnosis of LCIS. All were 〈50 years of age. All three cancers were in the same breast as the previous LCIS. Two women were treated by modified radical mastectomy, and the third had wide excision/axillary dissection followed by radiation therapy. They are alive and disease-free at 16, 82, and 116 months. Conclusions: Four of 51 women treated with observation alone after diagnosis of LCIS developed breast cancer. All were detected by screening at an early stage. LCIS appeared to be an incidental finding on biopsy of mammographic abnormalities. The policy of observation alone for the finding of LCIS spares women mastectomy. Furthermore, cancers that develop in follow-up are likely to be detected at an early stage and be amenable to curative therapy. Observation alone is appropriate treatment for women with LCIS.

Notizen: Abstract Background: Inflammatory breast cancer (IBC) carries an ominous prognosis. Before 1988, women with IBC at our institution were treated with neoadjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without vincristine and prednisone (CMF/VP). After 1988, women with IBC were treated with cyclophosphamide, doxorubicin, and 5-fluorouracil (FAC). This study compares these two regimens with regard to response and survival. Methods: The records of all women presenting between January 1973 and December 1991 with a stage IIIB (T4d, any N, MO) breast cancer with proven dermal lymphatic invasion by tumor cells were reviewed retrospectively. Results: The study comprised 38 women; 28 received CMF (22 CMF, 6 CMF/VP), and 10 received FAC. The overall response rate to induction chemotherapy in the CMF/VP group was 57% (40% PR, 17% CR), and 100% (60% PR, 40% CR) in the FAC group. The median overall survival for women receiving CMF/VP was 18 months compared with 30 months for women receiving FAC (p=0.02). The median disease-free survivals for the CMF/VP and FAC groups were 6 and 24 months, respectively (p〈0.001). When comparing responders and nonresponders with CMF/VP induction therapy, the responders had a significantly longer overall median survival (24 versus 10 months) (p〈0.001) and disease-free median survival (8 versus 2 months) (p〈0.001). All of the five patients remaining alive received FAC with 80% (four of five) having a complete response. These four patients subsequently underwent mastectomy and radiation. Conclusion: This study suggests that a doxorubicin-containing chemotherapy regimen improves overall and disease-free median survivals when compared with the previously used CMF combination in the treatment of IBC. A favorable response to induction chemotherapy also appeared to be associated with an improved survival.

Notizen: Abstract Background: Sentinel lymph node biopsy (SNB) in breast cancer may be used in place of axillary lymph node dissection (ALND) if SNB accurately stages the axilla. This study assessed the success and accuracy of axillary SNB with isosulfan blue (ISB) and technetium-99 sulfur colloid (TSC) compared to ALND. Methods: Forty-two women with T1 or T2 breast cancer underwent SNB and ALND. Sixty to 90 minutes before anesthetic induction, a mixture of 3 mL ISB and 1 mCi TSC was injected around the primary cancer or prior biopsy site. Intraoperatively, the SLN was identified using a gamma detector (Neoprobe 1000) or by visualization of the blue-stained lymph node and afferent lymphatics. The SLN was excised separately, and a level I/II ALND was completed. The histologic findings of the axillary contents and SLN were compared. Results: An axillary SLN was found in 38 of 42 (90%) cases. SLN localization rate and predictive value were the same for women who had and those who had not undergone excisional biopsy before the date of SNB. Fifteen of 42 (36%) patients had lymph node metastases. The SLN was positive in all women with axillary metastases (negative predictive value, 100%). Conclusions: If confirmed by larger series, a negative SNB may eliminate the need for ALND for select women with breast cancer.

Notizen: Abstract Background: The adequacy of excision of ductal carcinoma-in-situ (DCIS) usually is confirmed with specimen mammography and histopathological assessment of specimen margins. Postexcision mammography of the involved breast is used at some centers. The objective of this study was to evaluate the impact of postexcision mammography in DCIS. Methods: We conducted a retrospective chart review of all patients treated for DCIS at our institution from 1995 to 1998. Results: Sixty-seven patients had postexcision mammography performed. Residual microcalcifications were identified in 16 patients (24%). Further surgery was precluded by precise mammographic- pathological correlation by using sliced-specimen mammography in two patients. Twelve patients had repeat wide excision, and two patients underwent mastectomy. Residual DCIS was identified at re-excision in 9 of 14 patients (64%). The margin status of the initial resection was negative in three of nine patients (33%) and positive or unknown in six of nine patients (67%). Conclusions: Postexcision mammography is a valuable technique that complements specimen mammography and histopathological margin assessment in confirming that an adequate excision of DCIS has been performed. Postexcision mammography should be performed in all patients with DCIS associated with mammographic calcifications who are treated with breast-conserving therapy.

Notizen: Summary The surface modification of poly(ether-imide) by the photochemical vapour phase grafting of poly(2-hydroxyethylmethacrylate) is described. After grafting for four hours the contact angle of the film surface was 62° compared to a value of 80° for an untreated sample. XPS confirmed the presence of 2-hydroxyethylmethacrylate in the polymer surface.

Notizen: Abstract Expression of gelsolin, an actin filament regulatory protein, in human breast ductal carcinoma in situ (DCIS) was analyzed by immunohistochemistry using a monoclonal antibody. Formalin‐fixed paraffin‐embedded tissues from 59 pure DCIS specimens and 33 DCIS specimens with associated invasive components were evaluated for gelsolin reactivity and compared to eight normal breast cases and 76 invasive breast cancers. The proportion of cases exhibiting negative/low expression of gelsolin in the epithelium was as follows – normal, 0%; pure DCIS, 56%; DCIS associated with invasion, 58% in the DCIS component and 66% in the invasive component; invasive carcinoma, 70%. These data demonstrate that down‐regulation of gelsolin expression in breast epithelium frequently parallels progression to malignancy. Testing gelsolin expression (normal vs. negative/low levels) in the DCIS lesions for associations with patient age or any of the following histopathologic parameters revealed no significant (95% probability level) correlations – tumor size; pathologic (Van Nuys system) grade; nuclear grade; necrosis; presence of histologic calcifications; presence or type of adjacent benign lesions; architectural histologic pattern; and mammographic extent. Gelsolin loss was more commonly associated with mammographic soft tissue lesions as compared to calcified lesions (P = 0.009). A positive trend of borderline significance (P = 0.06) found in the DCIS with invasion group was a correlation between down‐regulated gelsolin expression in the DCIS component and size (〈 versus ≥ 15 mm) of the invasive tumor. In conclusion, reduced gelsolin protein is detectable in at least half of breast lesions which have progressed to DCIS. The trend between increasing gelsolin loss and malignant progression from normal epithelium to DCIS to invasive breast cancer (P 〈 0.0001) suggests additional investigation is needed to determine the potential of altered gelsolin expression as a marker for prognosis and for therapeutic interventions in breast cancer.

Notizen: Summary A prospective study was undertaken to evaluate associations among mammographic normal dense and fatty tissue, benign histologic findings, and cellular proliferative activity determined by DNA S phase percentages. Mammographic and histologic findings of benign, normal dense and fatty tissue contained in 100 excised specimens were cross-tabulated with flow cytometric DNA S phase percentages of needle aspirates obtained under radiographic guidance. Histologic evidence of atypia or hyperplasia was present in 21 (32%) of 66 fatty tissue samples and 11 (32%) of 34 dense tissue samples (p = NS). The median S phase percentages were identical for mammographic fatty and dense tissue (median % S phase = 5.35). The frequency of high S phase percentages (above the median) was not significantly different for tissue containing atypia or hyperplasia, 47% (15 of 32), as compared to tissue containing other benign histology, 52% (35 of 68) (p = NS). These frequencies were similar in women 49 and younger or 50 and older. These data show that mammographic normal dense and fatty tissues contain similar frequencies of histologic atypia or hyperplasia and low and high cellular proliferative activity determined by DNA S phase percentages in women aged 49 and younger and 50 and older.

Notizen: The preparation of a poly(maleimide-ether) containing pendent thiophene rings via the reaction of 2-(3-thienylmethyl)-1,3-N,N'-bis(3,4-dichloromaleimido) propane with 1,4-dihydroxybenzene is described. The novel 2-substituted-1,3-N,N'-bis(3,4-dichloromaleimido) propanes were obtained by allowing their corresponding diamine hydrochlorides to react with 3,4-dichloromaleic anhydride in acetic acid in the presence of sodium methoxide. The diamine hydrochlorides were prepared by the reduction of their respective diamides. The poly(maleimide-ether)s were fully characterized and 13C-NMR spectroscopy was used to confirm the microstructure of the materials. The properties of the thiophene substituted polymer are compared with model poly(maleimide-ether)s. Electrochemical studies indicated that the thiophene rings in the thiophene-substituted poly(maleimide-ether) were not electroactive. © 1992 John Wiley & Sons, Inc.