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Ann Thorac Surg 1998;66:1312-1317
© 1998 The Society of Thoracic Surgeons

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Original articles: cardiovascular

Coronary artery operation in patients after breast cancer therapy

^a Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel
^b Institute of Oncology, Rabin Medical Center, Petah-Tikva, Israel

Accepted for publication May 8, 1998.

Address reprint requests to Dr Vidne, Cardiothoracic Surgery, Rabin Medical Center (Beilinson Campus), Petah-Tikva, 49100, Israel

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Objective. The purpose of this investigation was to retrospectively study the outcome of patients undergoing coronary artery operation who were previously treated for breast cancer.

Methods. Between July 1992 and December 1996, 28 patients with a history of breast cancer underwent coronary artery bypass graft operation and were randomly matched against a noncancer group of similar size (n = 36) to allow for comparison of their preoperative characteristics, operative course, and postoperative outcome.

Results. The incidence of sternal wound infection was significantly higher in the cancer group than in the control group (25% versus 6%; p = 0.027). Postoperative noncardiac chest pain occurred more frequently in the cancer group than in the control group (52% versus 31%; not significant). In the study group, radiotherapy and recent myocardial infarction were the only two independent factors associated with sternal wound complications. Patients with a less than 17-year interval between the breast cancer therapy and the coronary artery operation had a higher incidence of sternal wound infection (46%) as opposed to patients with a longer time interval (7%; p = 0.028; odds ratio = 12). Sternal wound complications were more frequent in patients with a history of right-sided breast cancer (50%) compared with left-sided lesions (12.5%; p = 0.068; odds ratio = 7).

Conclusions. Coronary artery operation in patients after breast cancer therapy may be associated with an increased sternal wound infection rate. To decrease this risk of infection, an approach through a right thoracotomy, minimally invasive techniques, the use of skeletonized internal mammary artery, and broad spectrum antibiotic therapy may be considered.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Breast cancer and coronary artery disease are among the most frequent diseases of the adult female patient [1]. The incidence of both diseases is so high that they frequently occur synchronously or metachronously in the same patient. When coronary artery disease follows a treated breast cancer in the same patient, a number of as yet unsolved problems arise. First, it is still uncertain whether all patients or only selected cases of treated cancer should be offered coronary artery operation, and if selection is indicated, what are the criteria for this selection? [2]. Second, it has been suggested that the use of cardiopulmonary bypass (CPB) impairs the patient’s immune system so that the present sequence of events may result in recurrence of the original cancer [2]. Finally, there is concern that the consequences of previous chest radiation, with or without operation, might affect the course and outcome of coronary artery bypass grafting (CABG), particularly when the internal mammary artery (IMA) is used as a conduit for myocardial revascularization [3].

In an attempt to address these issues, we retrospectively studied the records of patients who had undergone coronary artery operation after breast cancer in our institution, randomly matching them against a noncancer group of similar size, and comparing their preoperative characteristics, operative course, and postoperative outcome.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Between July 1992 and December 1996, 2,700 patients underwent a cardiac operation in the Department of Cardiothoracic Surgery, Rabin Medical Center. All patients were computer registered, and of these a total of 36 female patients with a history of treated breast cancer make up the present study group. Twenty-three of them had undergone CABG, 5 required a combined approach that included CABG and a valvular operation, and 8 had undergone a valvular operation only. The charts of the study patients were reviewed for demographic data, diagnosis and approach to the original breast cancer, and preoperative, operative, and postoperative information related to the cardiac operation. Aspects of concern regarding the breast cancer included site and stage of disease, date of operation, the administration of radiotherapy or chemotherapy, and follow-up studies for recurrent or metastatic disease.

Preoperative notes regarding the cardiac operation concerned age, type of angina, New York Heart Association (NYHA) functional class, type of admission (emergency, elective, or semielective during hospitalization), the presence of associated diseases such as diabetes mellitus, hypertension, and recent or old myocardial infarction (MI), and left ventricular function studies.

The standard operative technique consisted of a median sternotomy, routine aortic and atrial cannulation, and nonpulsatile CPB with moderate systemic hypothermia (28°C). Cold crystalloid cardioplegia (10° to 12°C) and topical cooling were used for myocardial protection. The left IMA was used whenever possible. Routinely, after IMA harvesting and before performing the anastomosis, the free flow from the papaverine-dilated IMA was measured on CPB. For small coronary vessels, an IMA flow of 50 mL/min at a mean arterial pressure of 60 mm Hg was acceptable. For larger left anterior descending coronary arteries, flows of 100 mL/min and greater were required. Operative data of concern were primarily the type of surgical procedure (aortocoronary bypass, valve operation, or both), the number of vessels bypassed when CABG was performed, and whether the left IMA was used. No right IMA was used. Cardiopulmonary bypass time as well as cross-clamp time was reported.

Postoperative notes of interest included length of hospital stay, early infectious or noninfectious complications, delayed chest pain or ischemia, and the resulting new NYHA functional class.

The follow-up information was obtained by contacting the patient directly, by contacting his family physician, or by contacting family members. All patients who developed chest pain more than 3 months after the operation underwent a treadmill study or a thallium heart scan to confirm or exclude postoperative ischemia or angina.

To allow comparison of the clinical and operative courses, as well as the postoperative complications and outcome of the study group with a noncancer control group, a similar sized group (control group) was obtained from the computerized database of all our surgical patients. At the first stage, systematic randomization was carried out, reducing the total group to 270 patients, and at the second stage, by matching for age, risk factors, urgency of operation, and operative approach, the total number of the control group was reduced to 36 patients. The records of the control group were reviewed similarly to those of the study group. Parameters concerning breast cancer, radiotherapy, and chemotherapy were negatively reported (as 0) in the control group.

The collected information was entered into a study database as either continuous or categoric variables for comparative statistical analysis. Because our main interest concerned primarily CABG and eight of the cardiac operations were pure valvular procedures, they were excluded from the study, leaving our audit with 28 breast cancer female patients in the study group and 36 female patients in the control group.

Distribution of variables (normal or nonnormal) was studied by one-sample Kolmogorov Smirnov test. For comparison of the two groups, ² analysis and Fisher’s exact test were used when appropriate for quantitative data, and Student’s t test (for normal variables) or the Mann Whitney U test (for nonnormal variables) for quantitative data. Equality of variances in normally distributed variables was examined by the Levene test. For multivariate analysis the stepwise logistic regression was applied. Time interval curves were constructed using the Kaplan-Meier product limit method. For univariate time comparison, the log-rank test was used, and for multivariate time analysis, Cox’s proportional hazard model was used. A probability of 0.05 or less was accepted as statistically significant.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
All the breast cancer patients were in pathologic stage I or II. Most of them underwent radical or total mastectomy. In all of them radiotherapy was applied through anterior chest wall, axillary, and supraclavicular fields after the surgical procedure, and 50 Gy were administered to the chest. Before 1980 cobalt radiotherapy was used adding extra radiation to the parasternal fields (IMA lymph nodes); in 1981, linear accelerator radiotherapy was introduced, sparing the radiation to the parasternal fields, and since 1990, the procedures is planned by computed tomography-generated fields. Pathology and treatment characteristics regarding breast cancer diagnosis in the study group are presented in Table 1.

The postoperative course is presented in Table 4 and in Fig 1. The postoperative stay was comparable in the two groups. The remote complications, postoperative cardiac ischemia, new NYHA functional class, and mortality rate were similar in the two groups. Only the incidence of sternal wound complications was significantly higher in the group with treated breast carcinoma compared with the control group. Four of the study group patients underwent sternoplasty using the pectoralis major muscle flap. One patient had wires removed because of a chronic fistula and 2 patients had limited superficial wound drainage. In the control group 1 patient underwent sternoplasty and another had a minor sternal wound infection that needed drainage. Postoperative chest pain, negative for ischemia, occurred more frequently in the study group than in the control group (52% versus 31%) (see Fig 1), but the difference was not statistically significant.

View larger version (15K): [in this window] [in a new window]   Fig 1. Postoperative complications and mortality in the two groups.

Within the study group, in a follow-up period of 6 to 54 months (mean 30 ± 13 months) no recurrence of malignancy or metastases was noted and no death was caused by malignancy. The observed survival rate was comparable in the two groups; 89.3% for the study group and 91.6% for the control group (Fig 2). Sternal wound infection occurred in 3 of 4 patients with recent myocardial infarction (75%) and in 4 of 24 patients without this morbidity (16%; p = 0.037; odds ratio = 15). Patients operated on after recent myocardial infarction had postoperative intensive care unit stay that was not different from that of the remaining study group in terms of ventilatory time, increased need for inotropic agents, or increased postoperative pulmonary problems. Six of 13 patients with less than a 17-year interval between the breast cancer therapy and the coronary artery operation (46%) had sternal wound infection as opposed to 1 of 15 with a longer interval (7%; p = 0.028; odds ratio = 12). Of 10 patients with a history of right-sided breast cancer, 5 (50%) had sternal complications after CABG, whereas of 16 patients with left-sided breast cancer, only 2 (12.5%) had these complications (p = 0.068; odds ratio = 7).

View larger version (16K): [in this window] [in a new window]   Fig 2. Survival rate of the two groups after coronary artery bypass graft.

Based on these two factors and a statistical logic model, sternal wound complications could be predicted with a sensitivity of 75%, a specificity of 90%, a positive predictive value of 98%, a negative predictive value of 33.33%, and a total accuracy of 89%.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Arteriosclerotic cardiovascular disease and cancer are the most frequent diseases affecting the adult population [1] and surgical therapy is the main treatment modality in the majority of cases. When coronary artery disease follows a treated breast cancer, it raises the dilemma of correct therapy. Because resection of malignant tumors may be associated with a potentially short life expectancy, there is reluctance to perform major cardiac operations on patients with a history of cancer. The natural wide range of behavior of malignant diseases, the variable effectiveness of the different treatment modalities and their potential for cure, and the severity of cardiac complaints, as well as the spectrum of disease associated with cardiac ischemia, are the main factors to be considered in the approach to heart disease in a treated cancer patient. Finally, the life expectancy of the treated malignant disease on the one hand and the severity of the cardiac pathology on the other, are weighed against each other and dictate the approach. Patients with a promising potential for cure of cancer are those with a long disease-free follow-up period after cancer therapy, those with early staged or slowly growing cancers, or those with a completely negative workup for cancer recurrence or metastatic spread. When only these patients are managed surgically, CABG is seldom associated with recurrence of malignancy or metastases [2]. However it is questionable whether only these patients should be eligible for operation or whether the criteria for selection should be extended to include patients with cancer disease but with a reasonable prognosis.

In an overview of randomized trials of breast cancer patients with and without radiotherapy, Cuzick and associates [4], studying long-term results of breast cancer patients, observed a significant excess of deaths among patients given radiotherapy as opposed to those not given it. Cuzick and associates could not pinpoint the primary cause of this phenomenon and speculated about metastases and second primary tumors. Host and coworkers [5] and Haybittle and colleagues [6] noticed that cardiac disease was the main cause of death in patients with breast cancer treated by radiation and followed up for a prolonged period of time. Besides case reports on young women who died of coronary artery disease after mediastinal irradiation but with no conventional risk factors [7, 8], numerous comprehensive reports have been accumulating that discuss the increased mortality caused by cardiovascular disease observed in radiation-treated breast cancer patients [9, 10]. Because cardiac damage by irradiation was reported to be dose and field related, left-sided breast cancer was reported to be associated with a higher mortality caused by myocardial infarction compared with right-sided tumors [6, 11, 12].

In this present study we could not support the theory concerning radiation-associated coronary arteriosclerosis. Although all our patients received radiotherapy to their chest and were later followed up for 1 to 32 years (mean, 16 ± 9 years), their process of arteriosclerosis was in no way accelerated compared with that of the control group, and CABG was undertaken at a comparable age in both groups. Furthermore, our preoperative cardiac studies and operative reports did not indicate any unusual pathologic processes, excessive technical problems, or undue events that were associated with the ischemic condition or the harvesting and use of the IMA and that could have been caused by the earlier radiotherapy to the chest. The postoperative course of the study group was also comparable with that of the control group.

Sternal wound infection is a major complication of cardiac operations, occurring in 0.4% to 5% of cases [13]. A number of retrospective studies [13–15] reported it to be associated with diabetes mellitus, obesity, history of chronic obstructive pulmonary disease, bilateral internal thoracic artery grafting, prolonged operative time, administration of blood units, reexploration, and prolonged postoperative mechanical ventilation. The higher incidence of sternal wound infection observed in our study group as opposed to the control group (25% versus 6%) suggests that this complication might be induced by the chest radiation, by interfering with wound healing and making it more susceptible and vulnerable to infections. Furthermore, right-sided chest radiation was associated with a higher incidence of sternal wound infection than left-sided cases. This is explained by the fact that the radiation-induced devascularization effect on the right side of the chest was aggravated by devascularization induced by the harvesting of the left IMA. The net effect of these two processes was significantly reduced blood supply to the sternum [14], as if the two IMAs had been disconnected. This condition has already been reported to be associated with complicated sternal healing [15–17]. The reduced sternal blood supply may be further aggravated in the presence of other risk factors [18]. The problem of sternal devascularization induced by radiation could further explain the increased frequency of postoperative noncardiac chest pain observed in the study group. The increased risk of sternal wound complications associated with a shorter time interval between breast cancer therapy and CABG is an interesting finding open for speculation.

Preoperative angiographic assessment of the IMA and intraoperative flow measurements of the harvested IMA should precede every CABG procedure in patients with a history of radiation. The radiation-associated diseases of the IMA as well as the complications that followed CABG operations using the IMA in irradiated patients initiated an approach that avoided the use of the IMA [19, 20]. In spite of this, we and others [19] still prefer using the IMA as a viable conduit for myocardial revascularization procedures when intraoperative assessment shows good flow rates, because of its advantageous long-term patency [18, 19, 21]. The greater risk of sternal complications observed under these circumstances may be avoided by cardiac revascularization through a right thoracotomy [22], minimally invasive techniques, or use of skeletonized IMA or may be controlled by more aggressive antibiotic therapy or preventive elective sternoplasty.

Chemotherapy with 5-fluorouracil or cyclophosphamide was suggested to cause acute cardiac complications; however, long-term side effects have not been reported [23, 24] and were not observed in our present study.

In conclusion, radiation-treated breast cancer patients show a process of cardiac arteriosclerosis that is not different from that of nonirradiated patients. Patients operated on after being treated for breast cancer are expected to have an uneventful recovery that is not different from that of nonirradiated patients, either in terms of early or in terms of late cardiac complications. Their recovery may be associated with an increased sternal infection rate; because of this, an approach through a right thoracotomy, broad spectrum antibiotic therapy, and preventive elective sternoplasty may be indicated. With reasonable selection, the original cancer and its therapy does not jeopardize recovery from the CABG operation.

	References

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