Bilateral breast carcinoma: risk factors and outcomes for patients with synchronous and metachronous disease.

BACKGROUND: The aim of this study was to compare the outcomes of bilateral breast carcinoma (BBC) patients with those of patients who had unilateral disease. METHODS: From 1960 to 1995, 1465 Stage 0-III patients with primary breast carcinoma were treated with either mastectomy or breast conservation therapy at the Kimmel Cancer Center of Jefferson Medical College and Thomas Jefferson University Hospital. There were 1315 (89.9%) unilateral, 103 (7.1%) metachronous, and 47 (3.0%) synchronous breast carcinoma patients. Patients with synchronous breast carcinoma were defined as having a contralateral cancer diagnosed within 1 year of initial diagnosis. The percentage of patients with Stage 0-I disease at initial diagnosis was 49.4%, whereas 68% had Stage 0-I disease at subsequent diagnosis. For patients with metachronous breast carcinomas, the median interval between the first and second diagnosis was 44 months (range, 13-287 months). The median follow-up time was 58 months (range, 12-229 months) for patients with synchronous cancers and 87 months (range, 0.25-414 months) for those with metachronous cancers. Rates of overall survival and survival with no evidence of disease (NED survival), local control, and distant metastasis from the time of the second diagnosis were calculated for patients with synchronous and metachronous disease. These figures were then compared with each other and also with those for unilateral breast carcinoma patients. RESULTS: Patients with synchronous and metachronous breast carcinoma had worse 5- and 8-year NED survival rates compared with unilateral breast carcinoma patients, as well as an increased risk of distant metastasis. In multivariate analysis, differences in local control and overall survival were not statistically significant for patients who had bilateral disease compared with those who had unilateral disease. There was no difference when patients with metachronous and unilateral breast carcinoma were compared with respect to local control and overall survival. CONCLUSIONS: Patients with bilateral breast carcinoma who present with synchronous disease are at greater risk for distant metastasis than women with unilateral or metachronous breast tumors. There was a trend toward decreased overall survival and local control for patients with synchronous bilateral breast carcinoma compared with patients who had either metachronous or unilateral disease.

The number of positive margins influences the outcome of women treated with breast preservation for early stage breast carcinoma.

BACKGROUND: There are conflicting reports regarding whether focally positive surgical margins influence tumor control in breast-conservation therapy. The authors have evaluated the relation between positive surgical margins on tumor control and whether the number of positive margins affects tumor control in patients undergoing reexcision lumpectomy. METHODS: From 1978 to 1994, 453 American Joint Committee on Cancer Stage I/II breast carcinoma patients were treated at Thomas Jefferson University Hospital with breast conservation therapy. Patients underwent excisional biopsy and margin sampling with shaved biopsies of the tumor cavity. The entire breast received 45 grays (Gy) with a 20-Gy iridium-192 implant or an electron boost. Eighty-six patients had microscopically positive margins (19%), and the remainder had confirmed negative margins. The median follow-up time was 45 months. RESULTS: Local tumor control rates for patients with negative margins at 5 and 10 years were 94% and 87%, respectively, compared with 86% and 69%, respectively, for those patients with positive margins (P=0.005). The disease free survival rates for the negative margin group at 5 and 10 years were 91% and 82%, respectively, compared with 76% and 71%, respectively, for the positive margin group (P=0.001). Overall survival rates for patients with negative margins at 5 and 10 years were 95% and 84%, respectively, compared with 87% and 78%, respectively, for those with positive margins (P=0.047). When comparing the negative margin group with the one positive margin group, there was no significant difference in local tumor control (P=0.12). However, women with two or more positive margins had an inferior local tumor control compared with those women with negative margins (P=0.002). CONCLUSIONS: Patients with positive margins have a higher risk for local failure and worse survival when undergoing breast conservation therapy. Inferior local tumor control was noted in those patients with two or more positive margins.

Correlation of flow cytometry to clinical factors, hormone receptors, and histopathological grade in stage I and II invasive breast carcinoma.

DNA index (ploidy) and S-phase fraction (SPF) were measured by flow cytometry in 131 invasive stage I and II breast carcinomas. Ploidy showed a strong correlation with SPF (p = 0.0001), with aneuploid tumors having a high SPF. Both cytometric parameters correlated with tumor size and hormonal receptor status. Smaller tumors tended to be diploid and have low SPF. Nodal status did not demonstrate an association with cytometric findings. There was a highly significant connection between tumor grade, especially nuclear grade, and SPF (p = 0.0001). The study demonstrates the relationship between conventional prognostic factors, DNA content, and proliferative activity of breast tumors.

Ten-year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy.

BACKGROUND: One thousand seventy patients treated conservatively for Stages I and II breast cancer between the years 1982 and 1994 were reviewed. The median follow-up was 40 months with a maximum follow-up of 152 months. METHODS: All patients had a wide local excision and lower lymph axillary node dissection followed by radiation therapy. The entire breast received an external beam dose of 4500 cGy at 180 cGy/5 days/week. An additional boost dose of 2000 cGy to the tumor bed was given at the time of lumpectomy (perioperative) with an Ir-192 implant or with electron beam therapy after the external beam therapy. RESULTS: The 5- and 10-year disease specific survival results were 97 and 90%, respectively for Stage I and 87 and 69% for patients with Stage II disease. The 5- and 10-year local control rates were 93 and 85% for Stage I and 92 and 87% for Stage II, respectively. The risk factors for local failure were premenopausal status and estrogen receptor-negative status at the univariate level but at the multivariate level the premenopausal and margins status were significant. CONCLUSION: These 10-year results were at least equivalent to reported series of similarly staged patients treated by mastectomy. This should encourage more surgeons to offer conservative treatment as an alternative to mastectomy to patients with Stage I and II breast cancer.

Perioperative implantation of iridium-192 as the boost technique for stage I and II breast cancer: results of a 10-year study of 655 patients.

PURPOSE: To assess the efficacy of perioperative implantation of iridium-192 for stage I and II breast cancer. MATERIALS AND METHODS: The authors retrospectively reviewed findings from 655 patients with stage I and II cancer treated with conservative surgery and Ir-192 implantation between 1982 and 1992. Hollow plastic tubes were placed in the tumor bed as a single- or double-plane implant at lumpectomy. Ribbons with Ir-192 seeds were inserted into the tubes 4-6 hours later. The Ir-192 was left in place for approximately 50 hours. External-beam irradiation was given to the whole breast 10-14 days later. RESULTS: Follow-up ranged from 2 to 146 months. The local control at 10 years for stage I and II disease was 93% and 87%, respectively. The 10-year actuarial survival rate was 92% +/- 1 for stage I disease and 72% +/- 4 for stage II disease. The rate of survival with no evidence of disease for stage I and II disease combined was 82% +/- 1 at 5 years and 75% +/- 3 at 10 years. CONCLUSION: Perioperative implantation produced excellent local control equal to that with electron-beam therapy.

The role of radiotherapy in the treatment of breast cancer: results of perioperative implantation.

Between 1982 and 1993, 620 of 938 patients with pathologically staged I-II breast cancer were treated at the time of reexcision (perioperatively), with an iridium-192 (Ir-192) implant to the tumor bed to give 2000 cGy to the 30 to 40 cGy/ph isodose line. This was followed by 4500 cGy to the entire breast at 180 cGy/d for 25 fractions. The local control for the 620 patients at 5 and 10 years was 93 and 89%, respectively. The actuarial survival at 5 and 10 years was 92 and 81%. The cosmetic results were good to excellent for 87% of the patients. Chemotherapy had no impact on local control in this study. Ir-192 implant is especially useful for deep tumors, making possible more flexibility in the techniques used to boost the tumor volume. Perioperative implantation has increased the accuracy of placing the boost dose, shortened the overall treatment time, and, for some patients, eliminated the need for rehospitalization and anesthesia.

Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast.

BACKGROUND: Few women with locally advanced breast cancer remain disease-free, even for 2 years. Response to induction chemotherapy may be associated with longer disease-free and overall survival rates. The role of breast conservation in selected patients with response to induction chemotherapy was evaluated. METHODS: Since 1979, patients with Stages IIB and III breast cancer have undergone induction chemotherapy; patients with response continued chemotherapy until a plateau of regression was achieved. Before 1983, all patients having a response to chemotherapy underwent mastectomy; since 1983, selected patients have undergone breast conservation. Outcomes were tallied comparing these two groups of patients. RESULTS: The study group included 189 women, who were followed up for 12-159 months (median, 46 months) after diagnosis. Of the patients, 85% had a response to induction chemotherapy. Patients with no response were excluded from additional consideration in this study. One hundred three (64%) women underwent mastectomy; 55 (36%) were treated with breast conservation. The disease-free 5-year survival rate was 61% for all patients with a response to chemotherapy; 56% for those having mastectomy and 77% for those having breast conservation. The overall 5-year survival rate was 69% for all patients with a response to chemotherapy, 67% for those undergoing mastectomy and 80% for those having breast conservation. CONCLUSIONS: Induction chemotherapy achieves significant tumor regression in most women with locally advanced breast cancer, permitting subsequent breast conservation or mastectomy with a greater expectation of long-term success. Breast conservation is used more frequently with the same expectation of success as mastectomy, presuming careful selection based on response to chemotherapy.

A review of the role of radiation therapy in the treatment of patients with breast cancer.

Irradiation has been used to treat cancer of the breast since 1895. Over the period between 1895 to the present, the therapeutic use of irradiation has evolved from a cauterizing agent to a sophisticated use of theory and practice to cause tumor cell death while at the same time producing maximum normal tissue sparing. The use of radiation has made it possible for the surgeon to use conservative breast sparing surgery to obtain excellent cosmetic results, while at the same time producing a local control equal to that of mastectomy. For the patient, conservative surgery becomes a better option than mastectomy because it not only produces local control equal to that of mastectomy, but gives the wonderful added benefit of a more superior and pleasing cosmetic result.

A randomized phase III protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with brain metastases (RTOG-7916).

From 1979 through July 1983, 859 patients were enrolled in a Phase III RTOG Protocol (7916) evaluating the role of Misonidazole combined with radiation in the treatment of brain metastasis. Patients were randomized to one of four treatment arms (3.0 Gy x 10 fractions with or without 1 g/m2 of Misonidazole [total 10 g/m2] versus 5.0 Gy x 6 fractions with or without 2 g/m2 of Misonidazole) [total 12 g/m2]. Among the 779 analyzable cases, 63% had a lung primary and 12% had breast. Of the histologic types, 43% were adenocarcinoma and 24% were squamous cell. Seventy-eight percent had a Karnofsky of greater than 70. Of the 779 cases, 773 are dead (99%). Median survival is 3.9 months, with 60% alive at 3 months, 35% at 6 months, and 15% at 1 year. Survival was evaluated by treatment arm, Misonidazole status, and fractionation scheme; none showed any statistical significance. Favorable prognostic factors were assessed (age less than 60, Karnofsky of 70-100, controlled primary and brain metastasis only) in each treatment arm and no difference was found. Brain metastasis was cause of death in 1/3, and 19-33% of patients were retreated. Because up to 1/3 of the patients in this study died secondary to uncontrolled brain metastasis, improvement in local control remains an important goal. Until proven otherwise, the treatment of choice for the majority of patients still remains a conventional palliative course of 3.0 Gy x 10 fractions.

Computer-CT planning of the electron boost in definitive breast irradiation.

Treatment planning of the electron boost in breast irradiation at this institution is performed by using information from CT scanning and from surgical clips used to define the tumor bed. A refinement of this technique, taking into account the surgical axis of approach, using computer-CT planning is now implemented. The location of the scar and the clips are digitized using a computer to define the tumor bed dimensions. With 3-D computer software a line, simulating the surgical axis and the central ray of the electron beam, is drawn between the deepest clip and the surgical scar. This beam's eye view along the surgical axis is projected onto a screen as a starting point. Appropriate gantry angle, treatment table position, beam energy, and precise shaping of the electron field borders with a 2 cm margin around the clips and the scar are determined. Simulation films comparing clinically set-up fields and computer-CT planned fields were reviewed. In only 5 of 17 patients did the clinically set-up field have adequate inclusion of the tumor bed within the treatment volume. Computer-CT planned fields ensured adequate inclusion of the tumor bed in all, including the remaining 12. In 7 patients obvious increased sparing of normal breast tissue was seen with computer-CT planned fields. This technique enables accurate placement of a shaped electron field and further refinement of electron boost treatment planning. This is especially true in situations in which the tumor bed is located at a site distant from the lumpectomy scar rather than directly beneath it and in cases where the tumor bed lies deep within the breast.