Local recurrence in breast cancer: implications for systemic disease.

BACKGROUND: Recurrence in breast carcinoma follows a pattern of growth marked by local, regional, or widespread dissemination. Local recurrence may be the harbinger of systemic disease or failure of local control. Delineation of these processes may have implications in treatment. METHODS: A retrospective review found 1,171 patients with stages I and II breast cancer from 1978 to 1990 treated at the City of Hope Medical Center. RESULTS: Twenty-seven percent (n = 313) of patients developed recurrences. These were classified as local, including chest wall and regional nodes (n = 40), local and distant (n = 63), and distant (n = 210). Mean follow-up was 60 months. Multivariate analysis demonstrates tumor size was not different between the three groups, but the presence of positive lymph nodes was: local = 51%, local and distant = 78%, and distant = 64%. The disease-free interval was longest in the local group (42 months) versus the local and distant group (23 months) and distant group (39 months). Median survival was calculated from the time of recurrence: local = 90 months, local and distant = 26 months, and distant = 16 months. CONCLUSIONS: A group of patients with local recurrence have improved survival and do not develop distant disease. This group may benefit from aggressive surgical treatment to control local disease. These data suggest that a subset of breast tumors can act locally aggressive without metastatic potential.

The value of symptom directed evaluation in the surveillance for recurrence of carcinoma of the breast.

Specific postoperative tests used to diagnose recurrent carcinoma of the breast were evaluated for their ability to have an impact on the over-all course of the disease. Sixty-four patients with recurrent or new contralateral primary disease were divided into two groups based on the method of diagnosis. Those patients with a new complaint at an interval between scheduled follow-up visits and who went on to have tests to document a recurrence were categorized as interval follow-up. Those who were seen at a prearranged regular follow-up period and received tests as recommended by the attending physician or surgeon and had a documented recurrence were classified as routine follow-up. Thirteen patients presented with new contralateral primary disease and 51 with metastatic disease (16, bone; 13, lung; 11, local; three, liver, and eight, multiple). The median time to discovery of recurrence from the primary treatment was 29 and 28 months for the interval and routine groups, respectively. Ninety per cent of the failures occurred by 53 months. The survival time after recurrence was significantly greater in those patients diagnosed routinely (p = 0.003). However, the over-all survival time (from primary therapy to death) was only significantly improved for the routine group when the contralateral new primary diseases were included (p = 0.009). The method of diagnosis of a contralateral primary carcinoma was physical examination and mammogram. Strong recommendations for follow-up testing can be limited to mammogram and physical examination.

A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver.

Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02).

A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.

The ability of perioperative cefazolin to reduce the incidence of postoperative wound infection in patients undergoing ablative surgical treatment for carcinoma of the breast was tested in this prospective, randomized, double-blinded study. From May 1983 until December 1985, 118 women were divided into two groups at random. Group 1 consisted of 59 patients and received cefazolin and group 2 was made up of 59 patients who received a placebo. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. Three infections occurred among those in group 1 and five among those in group 2 (p = 0.72). The time to onset of infection was delayed in the patients in group 1 versus those in group 2 (17.7 days versus 9.6 days, p = 0.04). Six of eight infections occurred in patients in whom an interval between biopsy and definitive surgical treatment was present. Prophylactic antibiotics in mammary operations did not reduce postoperative wound infections in this study.

Central venous thrombosis related to the silastic Hickman-Broviac catheter in an oncologic population.

The use of subcutaneously implanted, Dacron cuffed, central venous silastic catheters (Hickman/Broviac catheter [HC/BC]) has not eliminated catheter related-central venous thrombosis (CR-CVT). HC/BC related CR-CVT was identified and followed in 15 oncology patients. Median time period to CR-CVT was 155 days (range 15-638). No correlation was established to patient age, sex, diagnosis, coagulation status, use, longevity, technique, or site of placement. Fourteen patients were treated with anticoagulation and/or thrombolytic therapy. Of seven patients treated with HC/BC in situ, one required HC/BC removal to achieve CR-CVT resolution. Median follow-up post-CR-CVT was 362 days (range 34-1622). No patient suffered untoward long-term sequelae. Nine patients had 11 catheters placed following resolution of CR-CVT. None had repeat thrombosis. CR-CVT incidence in a single 12-month period was 3.7% (7/190). The placement of HC/BC in an oncology population is an acceptably safe method for long-term venous access.

Evaluation of a short-stay program for patients undergoing mastectomy.

Two hundred twenty-eight patients were included in a retrospective study to evaluate the morbidity and feasibility of early discharge after mastectomy. Group I (early discharge, n = 75) patients were given pre- and postoperative instruction related to wound and drain care. Group II (concurrent control, n = 44) was given similar postoperative instruction, but received no preoperative teaching. Group III (historical controls, n = 109) underwent surgery during a period of more liberal hospitalization and discharge policies. The groups were similar in age, cultural background, operations performed, and pathologic diagnosis. Length of stay for groups I, II, and III was 5.5 +/- 0.4, 3.5 +/- 0.2, and 8.6 +/- 0.3 days, respectively. Groups I and II had a significantly shorter stay than group III. There was no difference among the groups for the presence of wound erythema, rate of primary healing, seroma formation, or wound infection. The practice of same-day admission and early discharge to limit length of stay for patients undergoing mastectomy is safe and effective.

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region.

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

Radiographic evaluation for pulmonary metastases in sarcoma patients.

The records of 130 patients with soft tissue and bone sarcomas were retrospectively analyzed to identify the subgroups of patients that would benefit from tomographic studies for pulmonary metastasis. Sixty-six of 96 patients with a normal conventional chest roentgenogram (CXR) had tomography to diagnose pulmonary metastasis. Of the 53 patients who had primary disease and a normal CXR followed by tomography, only 1 (1.9%) had metastases identified on tomograms. Of the 13 patients who had locally recurrent sarcoma and a CXR plus tomographic studies, 2 (15%) had metastases detected on tomogram only. Tomographic studies detected significantly more sarcoma patients with pulmonary metastasis in the group with locally recurrent disease than in the group with primary disease (P less than 0.05).

Predicting the need for prolonged enteral supplementation in the patient with head and neck cancer.

Nutritional support is an important consideration in the management of the head and neck cancer patient. In our series, characteristics significantly associated with the need for long-term postoperative nutritional support included stage IV cancers, primary pharyngeal tumors, combined treatment utilizing surgery and radiotherapy, and preoperative weight loss of more than 10 pounds. In planning nutritional support, nasogastric tube feeding is appropriate for short-term use. In contrast, gastrostomy tube feeding is preferable for those head and neck cancer patients with a high probability of requiring long-term nutritional support postoperatively.

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.

A prospective randomized trial was performed in patients with advanced squamous cell carcinomas (SCC) of the oral cavity, larynx, and pharynx to examine the effect of adjuvant postoperative radiation therapy on locoregional recurrence and survival following "curative" resection. Fifty-one patients with stage III or IV SCC treated from 1981 through 1984 were randomized to receive either surgery alone (n = 27) or surgery with postoperative radiation (n = 24). Five patients were excluded from the study after randomization because of ineligibility or protocol violations. Overall recurrence rates of 55.6% and 36.8% were noted in the surgery and surgery with adjuvant radiotherapy arms, respectively (p = NS). This trend towards a higher recurrence rate in the surgery only arm was in part due to the development of lymph node metastases in the contralateral, nonoperated neck. Thus far, no significant differences in either locoregional or overall survival have been noted between the two treatment arms. In this preliminary analysis, adjuvant postoperative radiotherapy does not appear to improve disease-free or overall survival.

Continuous hepatic artery infusion with an implantable pump: problems with hepatic artery anomalies.

The implantable pump for continuous hepatic artery chemotherapy requires even distribution of the chemotherapy to the whole liver for maximum efficacy. The hepatic arterial supply and its anomalies must be understood to achieve this. We reviewed the arteriograms of 100 patients who were potentially arterial perfusion candidates. Fifty percent had normal hepatic arterial anatomy. Twenty percent had a replaced or accessory right hepatic artery and 17% had an accessory or replaced left hepatic artery. The methods used to implant the pump catheters in these anomalous situations were reviewed. The use of dual catheter pumps for arterial anomalies has necessitated extended operative time and increased the risk of uneven hepatic perfusion. Catheterization of the portal vein, which is technically simpler, deserves consideration as an alternative in the presence of an aberrant arterial system.

Results of a prospective randomized trial of continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries.

One hundred patients were entered on a randomized prospective protocol to evaluate the effectiveness of hepatic resection of single as well as multiple hepatic metastases from colorectal primaries in combination with continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUDR) via the implantable pump (Infusaid, Intermedics Infusaid Inc., Norwood, MA). The eight patients with single metastases were randomized to hepatic resection alone (three patients) or hepatic resection plus CHAI (five patients). The 22 patients with resectable multiple metastases were randomized between receiving CHAI only (12) or CHAI after resection of all metastases (10). Patients who had positive portal lymph nodes (14) were all treated with CHAI. Patients with unresectable metastases (31) were randomized between intravenous 5-fluorouracil or CHAI of FUDR. FUDR was alternately infused every 2 weeks at a dose of 0.1 mg/kg/24 hour escalated to .3 mg/kg/24 hour with heparinized saline as the alternative infusate. The median follow-up of all patients was 20 months. All patients with multiple resectable metastases had at least a partial response (PR) to the CHAI (PR defined as greater than or equal to 50% decrease of the sum of the products of the diameters of the lesions measured on computerized axial tomography scans), and four patients given CHAI only had no metastases in the liver on relaparotomy. Patients with resection and CHAI had a better survival than patients with CHAI only; however, the difference was not significant. Patients with positive portal nodes and CHAI had a lower PR (36%) than patients with unresectable disease treated with CHAI (52%). Patients with positive portal nodes or metastatic disease outside of the liver did significantly worse than patients with unresectable disease treated with CHAI.

Inflammatory breast carcinoma: a distinct entity?

Sixty-four patients with the diagnosis of either inflammatory or locally advanced breast cancer were analyzed with respect to age, menopausal status, estrogen receptor protein (ERP) measurements, characteristics on clinical presentation, disease-free interval (DFI), and overall survival. There were no significant differences between the two groups in the patients' clinical presentation, DFI, or overall survival time. Patients with inflammatory carcinoma were significantly younger as well as more likely to be pre- or perimenopausal than patients with locally advanced breast cancer. Of those patients who had ERP measurements performed, patients with inflammatory breast cancer had a significantly decreased incidence of ERP(+) tumors in comparison to patients with locally advanced breast cancer. These results suggest that inflammatory carcinoma of the breast behaves as an ERP(-) subtype of locally advanced breast carcinoma rather than a truly distinct entity.

Complications of pelvic exenteration.

This report is based on a retrospective review of 104 patients who had undergone pelvic exenteration for advanced malignancy over a 29-year period (1956 to 1984, inclusive). Fifty-one patients (49%) developed major complications of the operative field involving the gastrointestinal tract (fistula or obstruction), the urinary tract (fistula, infection, or obstruction), or the wound (abscess, dehiscence/necrosis, or hemorrhage). No association was identified between the complication rate and organ of primary disease, extent of disease, tumor histology, or extent of resection. Patients receiving pelvic radiotherapy prior to exenteration had a much higher complication rate (39/58, 67%) than patients having had no radiotherapy (12/46, 26%). Reconstruction of the irradiated pelvis after exenteration by omental flap, colonic advancement, and/or myocutaneous flaps decreased the complication rate from 82% (27/33) to 48% (12/25). The operative mortality of pelvic exenteration was 2.9% and the actuarial five-year survival rate was 27%.

A prospective analysis of nosocomial wound infection after mastectomy.

We evaluated the postoperative course of all patients who had mastectomies from 1978 through 1982 at City of Hope National Medical Center (Duarte, Calif). The overall clean mastectomy wound infection rate was 24/294 (8.2%). The incidence of mastectomy wound infection varied with the method of biopsy and was 3.2% after needle aspiration and 9.5% after open biopsy. Mastectomy immediately after open biopsy ("one step") had an infection rate of 5.3%, whereas mastectomy at a subsequent procedure ("two step") had a rate of 12.4%. The maximal infection rate (23.0%) occurred following the two-step procedure when the interval was four to seven days. The infection rates for patients hospitalized three or more days before mastectomy were elevated, but no significant correlation was observed between the infection rate and other demographic factors. We recommend that needle aspiration biopsy be used prior to open biopsy to minimize the need for a two-step approach to mastectomy.

Use of right atrial catheter for prolonged iv support in cancer patients.

A right atrial catheter has proven to be a well-tolerated technical advance for patients requiring prolonged vascular access. It is easily inserted and suited for ambulatory maintenance by the patient. Catheters are utilized for a wide spectrum of iv medications with an acceptably low complication rate. Most significantly, the infection rate is negligible, despite severely compromised hosts. Their use should be considered for any patient in whom problems with vascular access are anticipated. This report comprises our experience with the first 70 catheters in 66 patients in the Hematology/Oncology service.

The use of a right atrial catheter in bone marrow transplantation for acute leukemia.

A right atrial catheter was implanted into 15 patients undergoing bone marrow transplantation as a treatment for acute leukemia. The catheter remained in position for 79 +/- 34 days. No catheter-related septicemia was observed. It appears that this catheter is helpful in supporting bone marrow transplant recipients.

Randomized sequential hormonal therapy vs adrenalectomy for metastatic breast carcinoma.

One hundred sixty-one postmenopausal and 65 premenopausal women, a total of 226 patients with metastatic breast carcinoma, were included in this randomized study to evaluate the merits of adrenalectomy as the primary mode of therapy as compared to the customary sequential hormonal manipulation. The 145 evaluable postmenopausal patients were randomized as follows: (1) primary additive hormone therapy first followed by adrenalectomy and (2) primary adrenalectomy followed by chemotherapy and/or additive hormone therapy. When 76 patients in group 1 were compared with 70 patients in group 2 regarding their survival time, there was no essential difference, but the response rate was 20% vs 38.6%, a significant difference. The 55 evaluable premenopausal women were randomized into two groups: (1) oophorectomy followed by adrenalectomy; (2) adrenalectomy-oophorectomy as primary mode of therapy. The response rate in group 1 was 17.4% as compared with 41.9% in group 2, but again there was no difference in the survival time among these two groups. When sequential hormonal manipulation was utilized, only one-third of these patients were subjected to adrenalectomy because of their rapidly deteriorating condition. Adrenalectomy performed as a secondary procedure showed a lower response rate but the total survival time was comparable with primary adrenalectomy patients.

Bilateral adrenalectomy for advanced breast cancer: a 21 year experience.

Of 680 patients who had bilateral adrenalectomies for metastatic breast cancer, 583 were evaluable. Two hundred and nine patients (36 percent) responded (180 objective, 29 subjective responders) for at least 6 months. Age, menstrual status, prior response to oophorectomy, disease-free interval, involved organ systems, and incidental splenectomy were correlated with adrenalectomy response. Patients aged 21 to 35 years did poorly (23 percent response rate), whereas 41 percent of patients aged 51 to 65 responded. Menstrual status appeared to have no effect upon whether or not a patient responded to adrenalectomy. Oophorectomy responders benefited from adrenalectomy 40 percent of the time and oophorectomy failures responded in 27 percent of the cases. Patients with a disease-free interval of zero to 2.5 years responded to adrenalectomy at a rate of 31 percent whereas patients with a free interval greater than 2.5 years responded at a rate of 50 percent. When a single visceral organ or any combination of bone and soft tissue was involved, the average response rate was 39 percent. However, when multiple visceral organs or a single visceral organ with any combination of bone or soft tissue was involved, the response rate dropped to 26 percent. Sixty-six patients had splenectomies at the time of adrenalectomy with a 44 percent response rate, whereas nonsplenectomized patients had a 35 percent response rate. The median survival rate of 209 adrenalectomy responders was 26 months; it was 10 months for 374 nonresponders. The 5 and 10 year survival rates for adrenalectomy responders were 18 and 7 percent, respectively, and zero percent for adrenalectomy nonresponders. The patients who received greatest benefit from adrenalectomy in this series were aged 51 to 65 years, had a disease-free interval greater than 2.5 years and had metastases limited to a single visceral organ or any combination of bone and soft tissues.