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Biomedical subjects

J L Connolly

Publications and source records attributed to J L Connolly.

At least 73 records · Page 4Linked to original sources
PubMed1991

Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome.

The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.

Actuarial Analysis↗
PubMed1990

Predictors of local recurrence following conservative breast surgery and radiation therapy. The influence of tumor size.

Size of tumor has not been established as a predictor of tumor recurrence in the breast following conservative surgery and radiation therapy. We analyzed 783 patients with infiltrating carcinoma treated with simple excision and radiation therapy. Median follow-up was 91 months. Median age at diagnosis was 50 years. There was a 13% recurrence among patients with T1 lesions compared with a 12% recurrence among patients with T2 tumors. Size did not predict for local recurrence when the tumor was analyzed by 1-cm increments and whether the tumor was estrogen receptor protein positive or estrogen receptor protein negative. Patients with an extensive intraductal component had a significantly higher local recurrence rate for every tumor size compared with patients with extensive intraductal component-negative tumors. We concluded that size did not predict local recurrence.

Breast Neoplasms↗
PubMed1990

Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy.

The identification of factors associated with breast recurrence following conservative surgery (CS) and radiation therapy (RT) is of potential use in refining patient selection criteria and treatment technique. In an attempt to define such factors we examined the relationship between various clinical, pathologic and treatment characteristics and the likelihood of breast recurrence in 783 patients with clinical stage I or II breast cancer treated between July 1968 and December 1982. Treatment consisted of complete gross excision of the primary tumor and RT to a total dose of at least 60 Gy to the primary site. During this period, pre-treatment mammograms and detailed histologic assessment of the margins of resection were not routinely performed. Median follow-up for surviving patients was 80 months. Thirteen patients (1.6%) were lost to follow-up. Ninety-one patients (12%) have developed a breast recurrence, corresponding to 5- and 10-year actuarial rates of 10 and 18%, respectively. The major feature associated with breast recurrence was the presence of an "extensive intraductal component" (EIC+). An EIC+ tumor was seen in 28% of evaluable cases with infiltrating ductal carcinoma and accounted for 60% of breast recurrences. Forty-three of 166 patients (26%) with EIC+ tumors developed a breast recurrence compared with 29 of 418 patients (7%) without an EIC (EIC-) (p = 0.0001). The 5-year actuarial rates of breast relapse were 24 and 6%, respectively (p = 0.0001). Very young age (defined as 34 years of age or younger) was also a significant factor associated with the risk of breast recurrence. Very young patients comprised 8% of the patient population and accounted for 16% of breast recurrences. Fifteen of 61 very young patients (25%) developed a breast recurrence compared with 76 of 722 older patients (11%) (p = 0.001). The corresponding 5-year actuarial rates of breast recurrence were 21 and 9% (p = 0.005). None of the other clinical or pathological factors examined by univariate analysis were significantly correlated with recurrence in the breast. A multivariate model of site of first failure (polychotomous logistic regression) also showed that EIC+ tumors and very young age were the main factors associated with a high relative risk of breast recurrence. We conclude that EIC+ tumors and very young age are associated with a high risk of breast recurrence for patients treated with limited excision prior to RT.

Actuarial Analysis↗
PubMed1990

Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells.

Somatic cell hybrids between MCF-7 human breast cancer cells and normal immortalized human mammary epithelial cells have been obtained by polyethylene glycol-mediated cell fusion. The hybrid cells are suppressed in their ability to form tumors in nude mice, as well as in traits specific to the tumorigenic MCF-7 parent: growth factor independence, tumor necrosis factor sensitivity, and pS2 gene expression. In addition, they display other characteristics of the "normal" parent, including increased expression relative to the MCF-7 cells of the genes for the extracellular matrix component fibronectin, the intermediate filament keratin 5, and the angiogenesis inhibitor thrombospondin. The levels of keratins 8 and 18 also resemble those of the nontumorigenic parent. These results provide evidence for the existence of tumor suppressor gene products in immortal mammary epithelial cells. We propose a characteristic "suppressed" tumor cell phenotype, which encompasses altered cytoarchitecture, angiogenesis capabilities, and growth factor requirements.

Animals↗
PubMed1990

The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast.

Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.

Breast↗
PubMed1989

Influence of infiltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy.

To determine the influence of infiltrating lobular histology on local tumor control, the authors studied 49 patients with Stages I and II infiltrating lobular breast carcinoma treated by limited excision of the tumor and radiotherapy between 1968 and 1981 (median follow-up, 75 months). Results were compared with those in 561 cases of infiltrating ductal carcinoma similarly treated during the same period. The 5-year actuarial risk of local recurrence was similar for patients with infiltrating lobular or ductal carcinoma when the latter was evaluated as a single group (12% versus 11%). However, the 12% 5-year actuarial local recurrence risk for patients with infiltrating lobular carcinoma was intermediate between that for patients with infiltrating ductal carcinomas with an extensive intraductal component (23%) and those without an extensive intraductal component (5%). The pattern of recurrence in the breast was similar in the infiltrating lobular and ductal groups. All recurrences in patients with infiltrating lobular carcinoma and 80% of recurrences in the infiltrating ductal group occurred in the vicinity of the primary tumor (P = not significant). None of the clinical or morphologic features examined significantly influenced the risk of local recurrence in patients with infiltrating lobular carcinoma. The authors conclude that combined conservative surgery and radiotherapy appear to be a reasonable treatment option for patients with infiltrating lobular carcinoma, but further follow-up will be required to confirm these results.

Adult↗
PubMed1989

Prognosis following local or regional recurrence after conservative surgery and radiotherapy for early stage breast carcinoma.

Factors which influence patient prognosis following a breast recurrence or regional nodal recurrence after initial treatment of early-stage invasive breast carcinoma with conservative surgery and radiotherapy are not well known. Ninety patients treated at the Joint Center for Radiation Therapy treated from 1968-1981 had a recurrence in the treated breast before (84) or simultaneous with (6) distant metastases. Sixty-five patients had salvage mastectomy (median subsequent follow-up in patients without further disease, 32 months; range, 1-123 months). The five-year rate of further recurrence in this group was 37%. The most important variable associated with subsequent outcome was the histology of the recurrent tumor. There were no further recurrences among 10 patients with purely non-invasive cancer or 10 patients with predominantly non-invasive disease and only focal areas of invasion. In contrast, 17/45 patients (38%) with predominantly infiltrating tumors suffered further local-regional recurrences (6) or distant metastases (11) following mastectomy (5-year actuarial rate, 55%) (p less than 0.05). Ten patients developed regional nodal failures without evidence of simultaneous breast recurrence (1 internal mammary, 3 supraclavicular, 1 both supraclavicular and axillary, and 5 axillary). Only 3 of these 10 (all with axillary node failures) did not have simultaneous distant metastases; they remain alive without evidence of further distant or local-regional recurrence following salvage treatment 1, 59, and 87 months after recurrence. We conclude that the great majority of the patients (88% in this series) who have a breast recurrence following initial conservative surgery and radiation therapy for early stage breast carcinoma will have disease limited to the breast clinically and tumors amenable to salvage mastectomy. Salvage mastectomy appears to be effective treatment for patients with an isolated breast recurrence, especially if the recurrence is predominantly or wholly non-invasive.

Adult↗
PubMed1989

Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast.

A small number of patients with early stage breast cancer are found on presentation to have two or more separate carcinomas within the breast. To assess the effectiveness of conservative surgery and radiation therapy in these patients we compared treatment outcome among 10 patients with multiple lesions (21 cancers) and 707 patients with single lesions, treated at the Joint Center for Radiation Therapy between 1968-1981. Median follow-up was 64 months and 75 months for the multiple and single lesion groups, respectively. In each patient with multiple lesions, both (or all 3) lesions had similar histologic features. Eight of these ten patients (80%) had an infiltrating ductal carcinoma (IDC) compared to 72% of patients with single lesions. Six of these 8 patients with IDC had at least 1 lesion with an extensive intraductal component (EIC), compared to a 33% incidence of an EIC in solitary lesions. All lesions were grossly excised. Radiotherapy was given to the entire breast in all patients, with the majority also receiving a boost dose to the tumor bed site. Four of the 10 patients with multiple lesions recurred in the treated breast (40%) compared to 77 of the 707 patients (11%) with single lesions (p = 0.019, Fisher exact test). In the six patients with multiple lesions who had an EIC, three developed a local failure. In comparison, 43 of 167 patients (26%) with a single lesion with EIC developed a local failure. In patients with multiple lesions, 0 of 2 with IDC without an EIC, and 1 of 2 with histologies other than IDC had recurrence in the treated breast compared to 19 of the 342 (6%) and 15 of the 198 (8%) patients with single lesions with similar histologic features, respectively (p = NS). These results suggest that the presence of 2 or more separate primary tumors in the breast is associated with a high likelihood of local recurrence after treatment with conservative surgery and radiation therapy, even when all identified tumors are grossly resected. This may reflect the common finding of an EIC in these tumors. We conclude that the use of conservative surgery and radiation therapy for patients with more than one primary cancer in the breast should be considered with caution.

Adult↗
PubMed1989

Premenopausal breast cancer patients treated with conservative surgery, radiotherapy and adjuvant chemotherapy have a low risk of local failure.

The use of adjuvant chemotherapy in premenopausal breast cancer patients with positive nodes is now routine, but the optimal local treatment of these patients is uncertain. To determine the effect of adjuvant chemotherapy on the likelihood of local recurrence as the first site of failure in premenopausal patients treated with conservative surgery (CS) and radiotherapy (RT), we examined the outcome of 74 patients treated with CS, RT, and adjuvant chemotherapy and compared it to the outcome in 192 patients treated with CS and RT alone. Adjuvant chemotherapy consisted of four or more cycles of either a doxorubicin-containing regimen or cyclophosphamide, methotrexate, and 5-fluorouracil. All patients were less than 50 years old, had UICC-AJCC Stage I or II breast cancer treated between 1968 and 1981, had gross excision of the primary tumor, and had a total radiation dose to the primary tumor bed of greater than or equal to 6000 cGy. Factors predicting for local recurrence, such as extensive intraductal carcinoma and age less than 35, were equivalent in the two groups. Women treated with adjuvant chemotherapy had significantly worse T- and N-stages than women treated with conservative surgery and radiotherapy alone: 61% versus 36% had T2 tumors (p = 0.0003), 34% versus 6% had clinically positive nodes (p less than 0.0001), and 97% versus 4% had pathologically positive nodes (p less than 0.0001). Despite the poorer prognosis of patients treated with adjuvant chemotherapy, within 5 years of diagnosis, 4% of patients who received adjuvant chemotherapy had their initial relapse in the breast and 24% had initial failure elsewhere, compared with 15% local failure first and 14% failure elsewhere first for those treated without chemotherapy (p = 0.01). We conclude that premenopausal patients with positive nodes treated with combined modality therapy (conservative surgery, radiation therapy, and adjuvant chemotherapy) have a low risk of local recurrence as a first site of failure. These results suggest a possible interaction between radiation therapy and chemotherapy in their effects on local tumor control.

Adult↗
PubMed1989

The predictors of distant relapse following conservative surgery and radiotherapy for early breast cancer are similar to those following mastectomy.

Although previous studies have indicated that the predictors of local recurrence following conservative surgery (CS) and radiotherapy (RT) are not the same as those following mastectomy, it remains unclear whether the predictors of distant relapse differ by local treatment modality. Clinical and pathologic features predictive of distant relapse for patients treated with mastectomy have been well established and include lymph node involvement, histologic grade, and peritumoral lymphatic vessel invasion (LVI). To study the influence of these and other factors on the rate of distant relapse in patients treated with CS and RT, we have identified a group of 438 patients treated between 1968 and 1981 who met the following criteria: primary tumor size less than or equal to 5 cm, excision of the primary tumor, infiltrating ductal carcinoma as the most aggressive histologic subtype, histology evaluable for the presence of an extensive intraductal component, and a dose to the primary site greater than or equal to 60 Gy. Estrogen receptor status was available in 58% of cases, 76% had an axillary dissection, and 23% were treated with adjuvant chemotherapy. With a median follow-up of 89 months, 107 patients (24%) developed a distant relapse. The 5-year actuarial freedom from distant relapse (FDR) was 80%. Stepdown Cox proportional hazards regression analysis identified several factors associated with a significantly (p less than 0.01) increased risk for distant relapse: positive lymph nodes, histologic grade, necrosis, and lymphatic vessel invasion. The magnitude of each effect was then examined with a lifetable calculation. Five-year freedom from distant relapse was 86% for the node-negative subgroup, 78% for patients with one to three positive nodes, and 45% for patients with four or more positive nodes. For histologic grades I, II, and III, 5-year freedom from distant relapse was 96%, 97%, and 75%, respectively. For necrosis scored as absent, scant, moderate, or marked, 5-year freedom from distant relapse was 90%, 78%, 77%, and 66%, respectively. For lymphatic vessel invasion scored as absent or present, 5-year freedom from distant relapse was 85% and 63%, respectively. We conclude that the clinico-pathologic predictors for distant relapse following conservative surgery and radiotherapy appear to be the same as those following mastectomy. This observation is consistent with the notion that distant relapse is caused by the presence of micrometastases at the time of initial patient sentation and is not greatly influenced by selection of local treatment.

Breast Neoplasms↗
PubMed1989

Can the clinical and mammographic findings at presentation predict the presence of an extensive intraductal component in early stage breast cancer?

The presence or absence of an extensive intraductal component (EIC) in early stage infiltrating ductal breast carcinoma has been considered to be an important factor in determining the extent of breast resection required prior to radiation therapy. It would therefore be useful if the presence or absence of an extensive intraductal component in a breast tumor could be predicted pre-operatively. To determine whether selected radiographic features might be correlated with whether or not a cancer is EIC+, we reviewed the pre-operative mammographic findings in 105 cases of Stage I and II infiltrating ductal carcinoma. Forty-one cases were EIC+ and 64 were EIC-. Both EIC+ and EIC- tumors were commonly detectable by mammography (93% and 83%, respectively, p = NS). EIC+ cancers, however, were significantly more likely to show microcalcifications with or without a mass compared to EIC- cases (83% vs 27%, p less than 0.0001). In particular, the presence of microcalcifications without a mammographic mass was more common for EIC+ cancers than EIC- cancers (34% vs 5% p = 0.0002). Conversely, a soft tissue mass without microcalcifications was seen mammographically in 56% of EIC- cases, compared to only 10% of EIC+ cases (p less than 0.0001). Predictive value calculations showed that the presence of microcalcifications in the absence of a mammographic mass conveys a 73% likelihood a cancer will be EIC+ (95% confidence interval = 39-94%). The positive predictive value of a mammographic mass or architectural distortion without microcalcifications for an EIC- cancer was 92% (95% confidence interval = 79-98%). We conclude that the mammographic findings may be useful pre-operatively in differentiating between patients with and without an EIC. Microcalcifications are much more commonly associated with EIC+ cancers than EIC- cancers, and the presence of an EIC- cancer without a mammographic mass is infrequent. Further characterization of the extent and pattern of microcalcifications might improve the predictive value of mammography in the pre-operative identification of patients with an EIC.

Adult↗
PubMed1989

In situ carcinoma of the breast.

In situ carcinoma of the breast is a proliferation of potentially malignant cells within the lumen of the ductal-lobular system and is classified as ductal or lobular in type. It has become an increasingly frequent clinical management problem, primarily because of its enhanced detection by screening mammography. In this paper, we discuss the problems in histologic diagnosis, the natural history, presentation, and options for management of these two forms of in situ carcinoma.

Breast Neoplasms↗
PubMed1989

Clinically occult ductal carcinoma in situ detected with mammography: analysis of 100 cases with radiologic-pathologic correlation.

One hundred consecutive cases of clinically occult ductal carcinoma in situ (DCIS) detected with mammography were retrospectively analyzed to determine the spectrum of mammographic appearances and to study pathologic correlations. Seventy-two percent of the lesions appeared as microcalcifications, 10% as soft-tissue abnormalities, and 12% as a combination of the two. Six percent of lesions were found incidentally in the biopsy specimen. On the basis of mammographic measurements, 22% of the lesions were 5 mm or smaller, and 75% were 20 mm or smaller. Thirty-five percent of the microcalcification clusters were categorized as predominantly casts (linear), 52% as granular, and 13% as granular with several casts. Related pathologic features included the location of the tumor within the ductal system, pattern of growth (histologic subtype), amount and distribution of calcium formation, and presence or absence of reactive changes. Women aged 49 years or less with DCIS were more likely to have microcalcifications and less likely to have a soft-tissue mass than women aged 50 years or more (P = .04). The authors conclude that there is a wide spectrum of mammographic appearances of clinically occult DCIS.

Adult↗
PubMed1989

Therapy of in situ cancer.

In situ carcinoma of the breast is divided into ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). These two entities have different morphologic appearances and natural histories. The traditional treatment of DCIS has been mastectomy, which has been shown to yield a very high cure rate. Other options include excision with or without radiotherapy. Preliminary evidence suggests that these techniques can be successful in the great majority of patients, with most treatment failures being manageable by salvage mastectomy. Careful observation of these patients appears associated with a low risk of breast cancer mortality and is generally the recommended policy.

Axilla↗
PubMed1989

Breast carcinoma metastatic to a meningioma. Case report and review of the literature.

We describe a patient who developed an intracranial mass that consisted of a meningioma and metastatic breast cancer. A literature review revealed 12 similar cases. In epidemiologic studies, the incidence of meningioma in patients with breast cancer is higher than expected. Both tumors are more common in women, have been reported to flare during pregnancy, and express hormone receptors. In a patient with breast cancer, an intracranial mass with radiographic features suggestive, but atypical, of a meningioma should be evaluated surgically. The lesion may represent a metastasis, a meningioma, or both.

Bone Neoplasms↗
PubMed1988

Differential expression of keratins 13 and 16 in normal epithelium, benign lesions, and ductal carcinomas of the human breast determined by the monoclonal antibody Ks8.12.

Previous electrophoretic analysis has indicated that keratins 13 and 16 (K13 and K16) are not present in normal human breast epithelium, but K16 is expressed in some ductal carcinomas (Moll et al., Cell, 31: 11-24, 1982). K16 may thus represent a marker for identifying a subset of ductal carcinomas and for distinguishing such tumor cells from normal cells. To explore this possibility further, we have used the monoclonal antibody Ks8.12, reportedly specific for K13 and K16 (Huszar et al., Differentiation, 31: 141-153, 1986), to examine keratin expression in human breast tissues. In immunocytochemistry the antibody reacted with epithelial cells of all normal samples, hyperplasias, and fibroadenomas. The staining was moderate to strong and always heterogeneous, involving most but not all luminal cells of ducts and acini. Myoepithelial cells were never stained. Of twenty-one ductal carcinomas examined, 90% gave a very weak or no reaction. The remaining 10% of cancers exhibited moderate to strong staining in about 50% of tumor cells. Cytoskeletal polypeptides extracted from the tissues and separated by polyacrylamide gel electrophoresis were analyzed by Western blotting to identify the polypeptides recognized by Ks8.12. In samples from normal tissue and a fibroadenoma, the antibody recognized a major Mr 48,000 component, a size appropriate for K16. In extracts from a hyperplasia and two of four carcinomas, the antibody detected a Mr 54,000 polypeptide, as well as a Mr 48,000 band, properties consistent with K13 and K16, respectively. Our results provide the first evidence indicating that K16 is present in normal as well as abnormal human breast epithelium. In addition, the data suggest that K13 may be expressed in some benign lesions and ductal carcinomas of the breast. Accordingly, Ks8.12 may prove to be useful for subclassifying ductal carcinomas and for discriminating between normal and certain benign and malignant disorders of human mammary epithelium.

Antibodies, Monoclonal↗
PubMed1988

The effect of young age on tumor recurrence in the treated breast after conservative surgery and radiotherapy.

Prognostic factors for local recurrence following conservative surgery and radiation therapy for patients with early breast cancer have not been fully established. To evaluate the importance of young age as a prognostic factor for local recurrence, we reviewed the results of treatment of 597 patients with 607 UICC-AJCC Stage I or II breast cancers, 47 of which were diagnosed when the patient was less than 35 years old. All were treated with excisional biopsy and a total dose to the site of the primary tumor of 60 Gy or more. The median follow-up in survivors was 63 months. Patient age and the presence of an extensive intraductal component (EIC) were both highly associated with the likelihood of tumor recurrence in the treated breast. Patients under 35 had an actuarial 5-year recurrence rate of 26%, compared to 10% for older patients (p = 0.002). Patients with an EIC had a breast recurrence rate of 25%, compared to 5% when EIC was absent (p less than 0.0001). Although the incidence of an EIC was higher in the younger subgroup (44% vs. 31%), this alone did not account for the difference in in breast recurrence rates, since younger patients had a higher recurrence rate than older patients even when an EIC was absent (22% vs. 3%, p = 0.0003). We conclude that the age of the patient is an important prognostic factor for local recurrence following conservative surgery and radiation therapy. This finding is in part attributed to the observation that younger women are more likely to have tumors with an EIC than older women, but even when an EIC is absent, they may be at an increased risk of local recurrence. However, caution is required in interpreting these findings with regard to selecting among treatment options until further data are available comparing the results of conservative surgery and radiation therapy to those of mastectomy in younger patients.

Adult↗