Charles McKhann

Ipsilateral breast tumor recurrence as a predictor of distant disease: implications for systemic therapy at the time of local relapse.

PURPOSE To evaluate the prognostic significance of ipsilateral breast tumor recurrence (IBTR) with respect to the subsequent development of distant metastasis. MATERIALS AND METHODS Between January 1970 and December 1989, 973 patients with invasive breast cancer were treated with conservative surgery and radiation therapy at Yale-New Haven Hospital. The median follow-up time as of December 1993 was 8.6 years. A number of prognostic factors were tested as possible predictors of distant metastases, including whether a patient experienced IBTR. IBTRs were broken down by time to recurrence to determine whether the breast recurrence-free interval had any prognostic relevance with respect to the development of distant metastasis. RESULTS As of December 1993, out of the entire population of 973 patients, 73 patients had developed IBTR and 134 had developed distant metastases. The overall actuarial survival rate at 10 years was .71 +/- .02, with a 10-year actuarial breast recurrence-free rate of .84 +/- .02 and a 10-year distant metastasis-free rate of .77 +/- .02. The overall distant metastasis rate was higher in patients who experienced IBTR compared with patients who had never experienced IBTR. Furthermore, the time to IBTR had a significant effect on distant metastases. Of 32 patients who developed an IBTR within 4 years of original diagnosis, 16 (50%) developed distant metastases. In contrast, of 41 patients who developed later breast relapses (> 4 years from original diagnosis), only seven (17%) developed distant metastases (P < .01). Of 32 patients who developed early breast relapse, the 5-year survival rate following breast relapse was .50 +/- .01, compared with a 5-year post-breast relapse survival rate of .78 +/- .10 among 41 patients with later breast relapses (P < .05). CONCLUSION It appears that early IBTR is a significant predictor for distant metastases. Whether early breast tumor relapse is a marker for or cause of distant metastases remains a controversial and unresolved issue. Implications for adjuvant systemic therapy at the time of breast relapse are discussed.

Prognosis following local recurrence in the conservatively treated breast cancer patient

At Yale-New Haven Hospital conservative treatment of early stage breast carcinoma with lumpectomy and radiation therapy has been used with increasing frequency since the 1960s. We have reviewed our experience with specific reference to prognosis following local recurrence. Between January 1962 and December 1984 a total of 433 patients were treated with conservative surgery and radiation therapy using standard techniques. As of December 1989, with minimum evaluable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 ipsilateral breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Extent of disease at the time of local recurrence was clinically categorized as localized (less than 3 cm without dermal involvement) or diffuse (greater than 3 cm and/or with dermal involvement). Seventy-two percent of the recurrences were at or near the original tumor site whereas 28% recurred elsewhere in the breast. At a median follow-up post recurrence of 5.0 years (range 0.3-16.9 years), the 5-year actuarial survival for breast recurrences was 59% and the 5-year disease-free survival was 65%. A number of clinical and pathological features at the time of original diagnosis as well as at the time of local recurrence were tested as possible prognostic indicators for survival following local recurrence. By univariate analysis, significant factors associated with survival following local recurrence included extent of local disease at the time of recurrence (p less than .01), time to local recurrence (p less than .03), with later recurrences doing better, and site of local recurrence (p less than .01), with recurrences elsewhere in the breast doing better. We conclude from this large single institutional experience with a median follow-up post-recurrence of over 5 years that patients experiencing a local recurrence in the conservatively treated breast have a relatively favorable prognosis. The prognostic factors correlating with survival and implications regarding adjuvant systemic therapy at the time of local recurrence are discussed.

A clinical and histopathologic analysis of the results of conservation surgery and radiation therapy in stage I and II breast carcinoma

One hundred eighty women with clinical Stage I or II operable breast carcinoma were treated by radiotherapy following local tumor excision at Yale‐New Haven Hospital through 1980. With a median follow‐up time of 6.9 years, the actuarial 5‐year overall and disease‐free survival rates were 82% and 78%, respectively. The 5‐year actuarial breast‐recurrence‐free survival rate was 92%. Several clinical‐histopathologic features and treatment parameters were assessed for their significance as predictors of local breast failure or distant relapse. Cox lifetable regression analysis showed that patients with clinical Stage II carcinomas had significantly worse overall and relapse‐free survival rates, but clinical stage alone had no effect on the rate of breast recurrence. Furthermore, a decrease in overall and disease‐free survival was evident when necrosis was present in the tumor or when patients had an infiltrating lobular carcinoma. Breast recurrence‐free survival was also influenced adversely by the presence of these two tumor features, especially when either tumor necrosis or infiltrating lobular carcinoma was found in conjunction with clinical Stage II lesions. Other histologic features such as grade, vascular invasion, perineural invasion, or the presence of an intraductal component of carcinoma did not affect outcome, nor did the treatment techniques employed appear to have a differential effect.

Reappraisal of the role of axillary lymph node dissection in the conservative treatment of breast cancer.

PURPOSE The purpose of this study was (1) to review systemic therapy practice patterns to assess how information regarding nodal status currently influences systemic therapy decisions, and (2) to review long-term outcome of patients who do not undergo axillary dissection compared with patients who do. METHODS AND MATERIALS For the current practice patterns portion of the study, the records of 292 patients who presented in the past 3 years with invasive breast cancer and underwent conservative surgery were reviewed to determine systemic therapy administered with respect to patient age, primary tumor size, clinical nodal status, and presenting symptoms. For the long-term outcome portion of the study, the records of 955 patients with invasive breast cancer who underwent conservative surgery and radiation therapy before December 1989 were reviewed. Patient characteristics and outcome of those patients who underwent axillary dissection (n = 565, 59%) were compared with a cohort of patients treated during the same era who did not undergo axillary dissection (n = 390, 41%). RESULTS For the current practice-patterns cohort, information regarding nodal status appeared to influence adjuvant systemic therapy for those patients less than 50 years of age and for those patients with palpable masses who were older than 50. Patients older than 50 with nonpalpable mammographically detected tumors have a low probability of nodal involvement and information regarding nodal status rarely changed therapy in this group of patients. In the long-term outcome study, there were no significant differences in the rates of distant metastasis, disease-free survival, or overall survival between those patients who underwent lymph node dissection and those who did not. CONCLUSION For selected patients, axillary lymph node dissection appears to have little influence on subsequent management and long-term outcome. These data suggest that it is time to reassess the role of axillary lymph node dissection in patients who undergo conservative surgery and radiation therapy.

Conservative surgery and radiation therapy in breast carcinoma: Local recurrence and prognostic implications

Conservative surgery with radiation therapy has been used with increasing frequency at Yale-New Haven Hospital since the late 1960s, resulting in a minimum evaluable follow-up time of 5 years on 278 patients treated prior to 1982. The radiation therapy technique generally encompassed treatment to the breast and regional lymph nodes of 4600 cGy with an electron beam boost to the tumor bed of 6400 cGy. Axillary dissection was performed in 19%, adjuvant chemotherapy in 7.3%, and adjuvant hormonal therapy in 5.7%; 65% were clinical Stage I and 35% were clinical Stage II. As of July 1987, with a minimum evaluable follow-up of 5 years and a median follow-up of 7.46 years, the actuarial 5- and 10-year survival for all 278 patients was 83% and 67%, respectively. The breast recurrence-free rate was 91% at 5 years and 80% at 10 years. Whereas the 5-year survival was significantly greater for clinical Stage I patients (91% vs 68%, p = .01), the breast recurrence-free rates did not significantly differ between clinical Stage I & II (93% vs 88%). There were 31 patients who failed in the breast alone as the first site of failure; 67% were at or near the primary site whereas 33% were distinctly removed from the primary site. Salvage mastectomy was performed in 25 patients, repeat wedge resection in two patients, and biopsy only in four patients. Axillary nodes were positive in five (33%) of 15 evaluable patients undergoing axillary dissection at the time of recurrence. The 5-year actuarial survival following local recurrence for the 31 patients was 48% at a mean follow-up of 5.06 years. The local recurrences were further subclassified into localized breast recurrences (LBR), defined clinically as greater than 3 cm and/or with dermal involvement. The 22 patients experiencing localized breast recurrences tended to occur later (median time to recurrence 4.3 years) than the nine patients experiencing a diffuse breast recurrence (median time to recurrence 2.9 years). At last follow-up, three (14%) of the 22 localized breast recurrences had subsequently failed distantly and none had subsequent local failure, whereas four (44%) of nine diffuse breast recurrences had subsequent distant failure and five (55%) of the nine diffuse breast recurrences experienced further local disease. The 5-year actuarial survival following salvage treatment was 90% for the localized breast recurrences and only 13% for the diffuse breast recurrences.

The rapid onset of cutaneous angiosarcoma after radiotherapy for breast carcinoma

Malignant neoplasms known to develop following external beam radiation include squamous cell carcinoma, osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, mixed mullerian tumors, malignant schwannoma, myelogenous leukemia and angiosarcoma. Latency periods of many years characterize the onset of these tumors following the exposure. Cutaneous angiosarcoma following radiotherapy for breast carcinoma has been rarely documented, occurring up to 13 years postirradiation. Two cases of this entity are reported occurring 37 months postradiotherapy at the site of mastectomy performed for mammary duct carcinoma.

Adjuvant systemic chemotherapy and hormonal therapy. Effect on local recurrence in the conservatively treated breast cancer patient

Background. The purpose of this study is to determine the impact of adjuvant systemic chemotherapy and adjuvant hormonal therapy on local relapse in the conservatively treated breast.

Subareolar breast cancer: Long-term results with conservative surgery and radiation therapy

PURPOSE It has been suggested that patients presenting with breast cancers within 2 cm of the nipple areolar complex represent a relative contraindication to conservative management due to either a compromised cosmetic result associated with sacrifice of the nipple areolar complex, reluctance to include the entire nipple areolar complex in the conedown field, or increased risk of multicentricity. We have reviewed our experience of conservatively treated patients with specific reference to the subset of patients presenting with tumors within 2 cm of the nipple areolar complex. METHODS AND MATERIALS Between January 1970 and December 1989, 1014 patients with early stage breast cancer were treated at Yale-New Haven Hospital by excisional biopsy with or without axillary lymph node dissection. Of the 1014 charts reviewed, a total of 98 patients fulfilled the criteria of having a central/ subareolar breast cancer. Reexcision was performed on only 16 patients. Following conservative surgery, patients were treated with radiation therapy to the intact breast to a total median dose of 48 Gy with conedown to a total of 64 Gy. adjuvant systemic therapy and regional nodal irradiation were administered as clinically indicated. RESULTS As of December 1993, the median follow-up for the 98 patients in this study was 9.03 years. The majority of patients had presented with either a palpable mass or a mammographically detected lesion. Three patients presented with Pagets disease, five with nipple discharge, and seven with nipple inversion. Ten of the 98 patients had the nipple areolar complex sacrificed at the time of surgery, while the remaining 88 patients had the entire nipple areolar complex included in the conedown field. Four of these 88 patients had the nipple partially blocked during the electron conedown. There were no significant complications associated with including the entire nipple areolar complex within the conedown field to a median dose of 64 Gy. Six of the 98 patients experienced a local recurrence, three experienced a regional recurrence, and nine experienced distant metastasis. The actuarial 10-year survival (0.79 +/- 0.06), distant disease-free survival (0.88 +/- 0.04) and breast recurrence-free survival (0.84 +/- 0.07) were not significantly different from those patients who presented with cancers in other parts of the breast. CONCLUSIONS Patients presenting with subareolar breast cancers within 2 cm of the nipple areolar complex are suitable candidates for conservative surgery and radiation therapy. In the majority of patients in this study, the nipple areolar complex did not need to be sacrificed and could be safely included in the electron conedown field with acceptable complications and cosmesis. A subareolar breast cancer does not represent a relative contraindication to conservative management in patients with early stage breast cancer.

Mammographically detected breast cancer. Results with conservative surgery and radiation therapy

At Yale—New Haven Hospital (New Haven, CT) treatment of early stage breast cancer with conservative surgery and radiation therapy (CS & RT) has been utilized with increasing frequency since the 1960s. The authors have reviewed their experience with specific reference to the outcome of those patients whose breast cancer was detected on routine screening mammography. To achieve adequate follow‐up, only patients treated before December 1984 are included in this analysis. Of 438 patients treated with CS & RT before December 1984, a total of 41 patients (9%) had nonpalpable lesions detected on routine screening mammography and were treated with CS & RT to the intact breast. Only two patients received adjuvant hormonal therapy and no patients received adjuvant systemic therapy. There has been only one breast failure and one death due to cancer in this group of patients resulting in actuarial survival and breast recurrence‐free rates of 100% at 5 years and 92% at 10 years. These results stress the importance of routine screening mammography and raise questions regarding the role of adjuvant systemic therapy in this selected group of patients.