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Background: For women with ductal carcinoma in situ (DCIS) of the breast who have been treated with breast-conserving surgery, the usefulness of size and surgical margin status (i.e., presence or absence of disease at the point of excision) as prognostic factors for predicting residual disease has not been well established. This study was conducted to determine more clearly the relationship between size and margin status of mammary DCIS to residual disease. Methods: The pathology records of 232 consecutive patients with mammary DCIS who had been initially treated with lumpectomy at the University Hospitals of Cleveland were retrospectively reviewed. The size of the DCIS and the surgical margins of lumpectomy were analyzed. Residual disease was defined as the persistence of DCIS in the re-excision and/or mastectomy specimens. Results: Residual disease was found in 15 of 101 patients with DCIS of less than 1.0 cm in longest dimension, in 27 of 96 patients with DCIS of 1.0-2.4 cm in size, and in 24 of 35 patients with DCIS of greater than or equal to 2.5 cm in size (P [is less than or equal to] .001). Residual disease was found in 30 of 77 patients with DCIS and positive margins, in 11 of 59 patients with DCIS and close margins ([is less than or equal to] 1 mm), and in 10 of 73 patients with DCIS and negative margins ([is greater than] 1 mm) (P = .001). In multivariate analysis, the occurrence of residual disease was associated with large tumor size (i.e., [is greater than or equal to] 2.5 cm) (odds ratio [OR] = 7.7; 95% confidence interval [CI] = 3.13-20.00; two-sided P = .0001) and with positive margin status (OR = 2.2; 95% CI = 1.02-4.55; two-sided P = .04). Conclusions: The size and margin status of DCIS each were found to be independent predictors of residual disease. [J Natl Cancer Inst 1997;89:1356-60]

BACKGROUND: Local recurrence following breastsparing surgery for breast cancer is no longer considered to be an ominous sign. Why this should be the case is not understood, and it poses a dilemma for the surgical oncologist. When does local recurrence represent an independent threat to survival? DATA SOURCES: I reviewed the few studies that have considered the size or tumor burden of locally persistent breast cancer, and the results of the Guy's Hospital Trials. CONCLUSIONS: Locally persistent breast cancer is seldom a risk to patient survival. The surgical literature is seriously deficient in its consideration of the tumor volume of locally persistent cancer. All available evidence suggests that a recurrent tumor is a risk only if its volume exceeds that of the original tumor. Patients appear to have a stable level of host defense against metastasizing tumor cells. Those who survive one breast cancer without developing distant disease can be expected to survive the local persistence of a similar volume of tumor. investigators should compare the size of each persistent lesion to the size of the patient's primary cancer. Excess deaths will occur only among patients whose persistent disease exceeds the volume of the primary. Am J Surg. 1996;171:445-448.

Background. The stratification of ductal carcinoma in situ (DCIS) of the human breast into prognostically relevant categories by size and histologic pattern is a current concern. Few studies have been able to follow women after the identification of any type of DCIS when they have had biopsy only. Methods. This is an extension of a follow-up study of a group of 28 women with small, noncomedo ductal carcinomas in situ that were excised by biopsy only, published in 1982. All these women have now been successfully followed for an average of almost 30 years. Results. The overall risk of development of invasive carcinoma for these women over almost 30 years is nine times that of the general population (95% confidence interval,4.7-17). This is similar to the l1-fold elevation in relative risk that was determined after about 15 years of follow-up. All invasive carcinomas have developed in the same area in the same breast. There were two women in whom invasive carcinoma developed between 20 and 30 years after initial biopsy. One other woman had an extensive noncomedo DCIS that was identified 25 years after her initial biopsy, but had no evidence of invasive disease. Conclusion. The natural history of small, noncomedo DCIS can last over at least 2 decades, with invasive carcinoma developing at the same site in which DCIS was previously discovered in a significant percentage of women (broadly, between 25%-50%). This is quite different from the natural history of comedo DCIS or any type of DCIS treated purposefully by surgery alone.

Background. The acceptance of local operative therapy for mammary carcinoma has stimulated scrutiny of specific techniques with the goals of minimizing the incidence of local recurrence while optimizing the cosmetic result. Intraductal spread of carcinoma has been established as a major factor in determining the rate of local recurrence after breast-conserving therapy for mammary carcinoma. The relationship of the anatomic location of a recurrent neoplasm to that of the primary tumor is likely to be instructive in evaluating the effectiveness of various proposed approaches to primary excision. Methods. Using the tumor registry of a tertiary care medical center, the authors reviewed all patients with mammary carcinoma treated with primary local excision during a 9-year period (1984-1992; n = 86), and identified all patients who subsequently experienced local recurrence (n = 5). The pathologic anatomic findings in each case were reviewed carefully and correlated with clinical and mammographic data. Results. The rate of local recurrence in this series was 5.8%, similar to that of Veronesi's 'lumpectomy' group (7%). In all five patients, the recurrent lesion was located in the same breast quadrant, along a radius from the nipple to the edge of the breast disc that crossed the site of the initial lesion. Conclusion. Local recurrence of mammary carcinoma after breast-conserving operative therapy most often occurs within the same segment; it is therefore proposed that its incidence may be substantially reduced with the use of a primary excision technique (based on normal breast anatomy) that removes en bloc the dominant tumor mass and the associated (possibly diseased) duct system. Cancer 1995; 75:1612-8.

Background: Local disease recurrences are a concern in conservative breast cancer surgery, and many studies have attempted to identify risk factors for these events. It is important to distinguish local recurrences linked to increased risk of distant spread from those due to inadequate local treatment. Purpose: We evaluated the incidence of local and distant recurrences according to demographic, biological, and pathologic variables in a large series of women who were conservatively and uniformly treated for breast cancer, with the aim of identifying women in whom local failure is predictive for distant metastases and who are therefore candidates for aggressive systemic treatment. Methods: Medical records of 2233 women who had been hospitalized at the Milan Cancer Institute from 1970 to 1987 were analyzed. All women received quardantectomy and axillary lymph node dissection followed by radiotherapy for the breast. Quadrantectomy is breast-conserving removal of most of the affected quadrant by a radial incision that includes part of the skin. The end points considered were local failures (including local recurrences and new ipsilateral carcinomas) and distant metastases. Statistical analysis employed the competing risks and multiple failures approaches. Results: There were 119 local recurrences, 32 new ipsilateral carcinomas, and 414 distant metastases as first events. The timing of local failures and distant metastases differed: The yearly probability for local failures was approximately 1% up to the 10th year and for distant metastases was 5% in the 2nd year and decreased progressively until the 8th year. Young age was an important risk factor, with peritumoral lymphatic invasion also predictive for local and distant recurrences. Tumor size and axillary lymph node involvement were not related to local recurrence but were important predictors of distant metastases. Extensive intraductal component was only a risk factor for local recurrence. Early (

Background. Breast reconstruction is performed with increasing frequency and has become important in the treatment of mastectomy patients. Methods. The development of recurrent carcinoma after a mastectomy and transverse rectus abdominus myocutaneous (TRAM) flap procedure is described. Results. The lesion was nonpalpable and was detected by mammography. Conclusion. This case raises questions about the practice of not performing postreconstruction mammography for detection of local recurrence after mastectomy. Cancer 1994; 74:2804-7.

Background. Although breast-conserving therapy (tumor excision, axillary node dissection, and postoperative radiation) for women with breast cancer yields survival and local recurrence rates comparable with those of modified radical mastectomy, studies suggest that postoperative radiation leads to capsular contractures and poor cosmesis in patients with breast implants. Methods. The authors followed 20 women in whom breast cancer developed after augmentation mammoplasty (14 subcutaneous implants and 6 retromuscular implants). Average age at diagnosis was 52 years (range, 34-72 years). Most (55%) of the patients had tumors in the upper outer quadrant. Fifteen lesions were palpable and five were nonpalpable. All tumors were excised using wide margins that attempted to include a rim of normal breast tissue. Three patients had microscopically positive margins. The predominant histology was ductal adenocarcinoma (85%). The mean greatest tumor dimension was 1.43 cm; 75% were T1 lesions. Levels I and II axillary lymph node dissection revealed metastases in five patients. After surgery, six patients received systemic chemotherapy, and all patients received 4500-5000 cGy of tangential photon radiation delivered to the whole breast, plus a 1400-2100 cGy boost delivered to the tumor site using photon radiation, electron radiation, or iridium 192 implantation. Results. At a median follow-up of 3.8 years (range, 6 months to 9.3 years), there were no local recurrences; however, in two patients distant metastases developed. Seventeen (85%) of the twenty patients had good or excellent cosmetic results as determined by the degree of capsular contracture, breast shape and appearance, and the presence of skin changes. Conclusions. The authors conclude that breast-conserving therapy is a cosmetically acceptable therapeutic option for women in whom breast cancer develops after augmentation mammoplasty.

Background: Local or regional recurrence of breast cancer occurs in 5% -30% of patients treated by Halsted radical or modified radical mastectomy. Lag time between treatment and recurrence varies widely, and it is not known whether the recurring tumor grows at a constant growth rate or at a more rapid rate after a period of tumor dormancy. Purpose: This study was undertaken to discriminate between the above-mentioned hypotheses, i.e., determine whether a tumor that recurs after mastectomy grows at a constant rate or whether it grows rapidly following a period of tumor dormancy. Methods: A series of 122 patients with local recurrence as a first event after mastectomy for resectable breast cancer was evaluated. We measured the diameter of the recurring tumor (Dr) in each patient and calculated the diameter that the recurring tumor could have reached at the immediately preceding physical examination (Dpe), when no local relapse had vet been detected, by assuming an exponential growth during the treatment-free interval. For patients who had a calculated diameter Dpe that was large enough to have been detected at the previous examination, we assumed that a tumor 5 mm in diameter had been mistakenly missed, and the expected corresponding tumor diameter at the time of detection (Drc) was calculated. Finally, the minimum growth rate (mGR) consistent with the sequence 'no detection [arrow right] recurrence of diameter Dr' was obtained by assuming an exponential growth from the tumor volume corresponding to a diameter 1 mm less than the diameter detection threshold. Results: A wide overlap between Dr and Dpe values was observed. Seventy-two 591/c,) of 122 Dpe values were larger than the minimum Dr; 18 (15%) were even larger than the median Dr value. The difference between expected and observed detection rates was highly significant (P

Background. A number of factors concerning the prognosis of cancer patients have been reported, but the evaluation of individual factors is not always consistent. The author considered that the discrepancies may lie in part in that factors may have a changing influence on relapse with time. The present study was intended to reveal the phenomenon and its clinical significance in patients with breast cancer. Methods. Eleven pathological prognostic factors in 462 patients with primary breast cancer were analysed with special reference to the influence on relapse and its changes with time. The Cox regression analysis was performed for whole and three stratified non-overlapping observation period (within 2, 2-5 and 5 years more), using factors including extent of nodal involvement (N), nuclear grade (NG), tumor infiltrating lymphocytes (TIL), tumor size, fat infiltration (F) and others. Results. Cox regression analysis for whole observation period showed N followed by NG, TIL, F and others as the most important factors on relapse. But the analysis performed for 3 stratified intervals revealed that the influence on relapse decreased with time for N and NG, but tended to increase with time for F. The suppressive effect of TIL on relapse was not evident up to 2 years but was significantly emphasized after 2 years postoperatively. Conclusions. In conclusion, a distinct time-dependency with varied patterns was found in the influence of some prognostic factors on relapse, which implies the assessment of prognostic factors may vary according to the length of the observation period.

Background and Methods. Predictors of distant relapse following conservative surgery for breast cancer were studied in a review of 425 women. Five steps of breast cancer patient management were defined in which increasing amounts of information, potentially relevant to prognosis for metastasis-free survival (MFS), were available: (1) clinical, (2) biopsy, (3) tumorectomy, (4) axillary dissection, and (5) adjuvant treatments. At each step, a prognosis study based on the Cox model was carried out using all acquired information from the first step. Results. Among the 21 studied variables, 5 were independent stable risk factors in predicting MFS: (1) clinical node status, (2) modified Scarff-Bloom-Richardson (MSBR) histoprognostic grade, (3) progesterone receptor (PR), (4) anatomic tumor size, and (5) histologic lymph node status. These factors were progressively identified throughout the successive prognostic analyses and kept their significance at the reference step (axillary dissection step where all information is acquired). According to the prognostic score based on the significant variables, a stratification of the patients had been built at each step, identifying three risk groups (low, moderate, high). Even at biopsy step, the mere knowledge of clinical information, such as clinical node status, and biopsy information, such as MSBR grade and PR status, would enable 68% of the patients to be well classified according to the stratification of reference. Knowledge of an additional factor, such as anatomic tumor size, would bring the rate up to 88%. Some subsets of patients with stable prognosis throughout the steps were identified and their profiles were described. It is noticeable that 95% of the patients, classified low risk at the biopsy step, were patients that were stable. Conclusions. The early recognition of patients, highly curable by local therapy alone, would obviate aleatoric neoadjuvant treatment.

Background. This analysis was conducted to evaluate the impact of selected clinical, histopathologic, and flow cytometric factors on sites of initial tumor relapse after postmastectomy adjuvant systemic therapy. Methods. Five hundred sixty-four patients with axillary node-positive breast cancer were entered in two prospectively randomized trials and received cyclophosphamide, 5-fluorouracil and prednisone with or without tamoxifen as sole adjuvant therapy. These patients were studied to assess the risk of locoregional recurrence and to identify factors that might predict tumor relapse site. Results. With a median follow-up of 9.3 years, the 8-year cumulative incidences of initial locoregional or distant relapse were 20% and 35%, respectively. Pathologic tumor stage, estrogen receptor content, and number of involved axillary nodes were independent predictive factors for an increased risk of locoregional recurrence. With the exception of tumor stage, these factors also were associated with an increased risk of distant relapse so that tumor stage (T3a) remained the sole factor predictive of increased relative risk for initial locoregional (versus distant) recurrence in patients with tumor progression. Clinical and flow cytometric factors were not predictive of initial locoregional or distant relapse. Conclusions. Exploratory data analysis of two prospective trials of postmastectomy adjuvant systemic therapy has demonstrated a significant risk for initial isolated locoregional recurrence in certain patients with node-positive breast cancer. The benefit of improved locoregional tumor control in appropriately selected patients with axillary node-positive breast cancer who receive adjuvant systemic therapy requires additional investigation.

Background. Local recurrence is one of the major problems in treatment of breast cancer. Approximately 20% of patients who have radical or modified radical mastectomy have a local recurrence. Methods. The records of 98 women with locally recurrent breast cancer treated with wide local excision, in the years 1983-1987, were reviewed. The median age at excision was 62 years (range, 32-84 years). All patients were observed until death or December 31,1989. The median follow-up period was 36 months (range, 2-79 months). Results. At follow-up, 44 of 98 patients (45%) had had a new local relapse and 47 of 98 (48%) were dead. The median duration of local control for all patients was 21 months (range, 1-79 months). The diameter of the local recurrence seemed to influence the duration of local disease control but not total survival. Patients admitted directly for surgery had a longer period of local control compared with patients admitted after unsuccessful oncologic treatment of the local recurrence. The 5-year local control rates were 50% and 24%, respectively (P > 0.92). No statistically significant difference in local control could be shown whether or not the patient received additional oncologic therapy in continuity with the wide local excision. The 5-year local control rate in patients treated only by surgery was 33% compared with 42% in patients also receiving additional oncologic treatment (P > 0.63). Conclusions. Wide local excision of recurrent breast cancer seems to provide as good or even better local control than other treatment modalities. Surgery should not be postponed in cases of ineffective medical treatment or radiation therapy.

Background. The antihelminthic drug levamisole (LMS) is used in conjunction with 5-fluorouracil (5-FU) as adjuvant therapy to reduce the incidence of colon cancer relapse following surgical resection. Clinical trials in patients with breast cancer have yielded conflicting results as to its efficacy in the treatment of this malignancy. LMS is thought to act as an immunostimulant, yet its precise mechanism remains unclear. In this study, the effect of LMS on major histocompatibility complex (MHC) class I (MHC I) and MHC class Il (MHC II) expressions in human colorectal and breast carcinoma cell lines was examined. Methods. The colon cancer cell line CaCo-2 and the breast cancer cell line MDA-MB-435 were cultured for 24-68 hours in the presence or absence of 10-[mu] LMS followed by staining with antibodies directed against either MHC I or MHC II. After staining, cells were visualized by fluorescent microscopy. Results. When cultured in the presence of LMS, cells from both cell lines exhibited a decreased fluorescent intensity with antibodies directed against MHC I protein. The most significant difference from cells cultured without LMS was apparent after 48 hours of incubation. Neither cell line exhibited fluorescent intensities above background when stained with anti-MHC II anti-body. Conclusions. LMS decreases the expression of MHC I on CaCo-2 and MDA-MB-435 tumor cell lines. Prior studies have indicated that natural killer (NK) cells are more efficient in attacking cells with lowered or no MHC I expression. An MHC I deficiency induced by LMS would augment NK-mediated immune surveillance. One mechanism contributing to levamisole's anti-tumor activity in vivo may be reduction of MHC I expression on tumor cells.

Background. Cell cycle kinetic measures have been shown to have prognostic significance in breast cancer. Methods that have been used to assess the proliferating fraction of tumors include measurements of DNA content with S-phase calculation by flow cytometric analysis, radioisotope-labeled nucleotide incorporation, and cell cycle-associated protein expression. The recent discovery of the S-phase-specific nuclear protein proliferating cell nuclear antigen (PCNA) opens the door for a novel approach to cell kinetic measurement with an immunocytochemical assay. Methods. A quantitative immunocytochemical assay for PCNA was performed on 82 primary invasive breast carcinomas fixed in formaldehyde solution and embedded in paraffin and 18 corresponding axillary metastases. The percentage of tumor cells with strong nuclear staining was determined by visual count. This PCNA score was correlated with histologic parameters, age, relapse intervals, and long-term survival. Results. PCNA scores were distributed normally among primary carcinomas (range, 5-54; mean, 22.5). Carcinomas had much higher scores than adjacent normal epithelium (means, 22.5 and 4.1, respectively; P < 0.0001), and axillary node metastases had slightly higher scores than corresponding primary breast tumors (means, 26.4 and 22.5, respectively; P = 0.05). The PCNA score did not correlate with age, tumor size, axillary node status, intramammary lymphatic-vascular invasion, or estrogen and progesterone binding capacities. Furthermore, its variability could not be explained by grade. PCNA values increased as the mitotic rate increased. Cancers with high PCNA scores ([is greater than or equal to] 25) were associated with shorter disease-free (P = 0.007) and overall survival times (P = 0.01) than tumors with low PCNA scores (< 25) (median follow-up, 166 months). Conclusions. PCNA score has potential value as a prognostic indicator in breast cancer. This method of assessing the proliferating pool offers advantages over other assays in terms of relative simplicity of the method, applicability to paraffin-embedded fixed tissue, and low cost.

Background. Optimal management of ductal carcinoma in situ (DCIS) of the breast is a problem that is occurring with greater frequency, mostly because of the increasing use of mammographic screening. The traditional role of mastectomy for DCIS has been challenged by breast-conserving procedures. Regardless of the method of treatment used, local control with complete tumor eradication is the major goal in the management of DCIS. Methods and Results. A patient is reported in whom DCIS recurred in residual breast tissue in the chest wall several years after mastectomy. Conclusions. Chest wall recurrence of DCIS within residual breast tissue probably is caused by failure of tumor excision, new primary tumor, or both. This observation underscores that (1) mastectomy may not result in complete removal of breast tissue, and (2) this residual breast tissue may be the substrate for 'chest wall recurrences' in some patients with breast cancer. Cancer 1993; 71:3025-8.

Background. Locoregional recurrences occur commonly in women with breast cancer and often have grave prognostic implications. Major controversies exist concerning the prophylaxis, implications, and treatment of such relapses and are the focus of this review. Methods. The relevant medical literature was reviewed and analyzed. Results. Locoregional recurrences may be prevented by postoperative radiation therapy; however, this has little impact on survival. Postoperative systemic therapy prevents locoregional relapse, but less efficiently than radiation therapy. When these modalities are combined, radiation therapy often is delayed until after several cycles of chemotherapy. Optimal sequencing remains controversial. Most patients with locoregional relapses have an exceedingly poor outlook. Radiation therapy provides excellent local control; however, the addition of combination chemotherapy should be considered for patients with defined poor prognostic features. The clinical impact of recurrence in the breast after breast-conserving primary treatment now is emerging. Such local relapses do not have the dreaded prognostic implications of locoregional relapse after mastectomy, but are a marker for an increased risk of dissemination. Standard therapy in this setting remains mastectomy. Additional breast-conserving surgery may be considered in the context of clinical trials for patients with certain favorable features. Conversely, some local relapses after breast-conserving surgery have a poorer prognosis, and the addition of adjuvant systemic therapy should be considered in addition to mastectomy. Conclusions. The heterogenous nature of locoregional relapses has made it difficult to conduct prospective randomized clinical trials. However, many retrospective data exist, making it possible to recommend rational treatment approaches for these patients. Cancer 1993; 71:2395-409.

Background. A second primary tumor (SPT) in the breast is the most common one seen in clinical practice. There are conflicting reports regarding the incidence and survival of patients with SPT in the breast. Methods. To elucidate this, data on 139,932 patients with primary breast cancer, reported to the Surveillance, Epidemiology, and End Results Program between 1973 and 1986, were analyzed. Of these, 3431 patients had a contralateral metachronous breast cancer (interval, > 6 months). Results. Survival from the date of diagnosis of the metachronous breast tumors was compared with that of patients with single breast tumors, controlling for age at diagnosis, stage, race, and treatment. In the multivariate analysis, age and stage at diagnosis of first and second tumors were the only variables that significantly influenced survival. The survival of patients with localized SPT was similar to that of patients with a localized single breast tumor. Patients with regionally advanced SPT lived for a shorter time than did corresponding patients with only one tumor. Conclusions. Patients with single breast cancer were at increased risk of having a SPT in the breast. As a result, efforts for early detection by physical examination and mammography of survivors of single breast cancer are advocated because the survival of patients with a localized SPT in the breast is as good as that of those with a single localized tumor. Cancer 1993; 71:172-6.

Background. The value of circulating CA 15-3 levels was assessed in 129 patients with recurrent breast carcinoma. Methods. Patients were divided into four subgroups, according to the following: Group A, locoregional recurrence alone; Group B, locoregional and subsequent systemic recurrence; Group C, combined locoregional and systemic recurrence; and Group D, differing sites of systemic disease. Results. One of 14 patients with locoregional disease alone had increased levels of CA 15-3 (> 25 U/ml). However, 96% of patients (22 of 23 patients) with combined local and systemic disease had increased tumor marker levels. The difference in CA 15-3 levels in patients with combined disease compared with patients with local disease alone was statistically significant (117.0 versus 17.5 U/ml, respectively; P < 0.02). Twenty-four patients with locoregional recurrence later had distant metastasis develop. In this group, patients with an increased CA 15-3 value had a significantly shorter lead time to the development of distant metastases compared with patients with normal tumor marker levels (20.8 [+ or -] 3.3 versus 10.3 [+ or -] 2.7 months, respectively; P < 0.03). CA 15-3 values at diagnosis were increased in 88% of 115 patients with metastatic disease. There was no significant difference in CA 15-3 levels among metastases to lung, liver, and bone nor was there any difference between single and multiple sites of distant metastasis. CA 15-3 is an excellent marker for systemic recurrence of breast carcinoma. Conclusions. Increased levels and no clinical evidence of recurrence strongly indicate the presence of occult metastatic disease. Cancer 1992; 70:2831-4.

Background: Our previous study of thymidine kinase (TK) levels in the serum of breast cancer patients demonstrated a statistically significant positive correlation with cancer stage. In postsurgical follow-up studies of 20 patients with primary breast cancer, total serum TK levels rose with disease recurrence and continued to rise with disease progression but decreased with treatment response. Purpose: This study was designed to examine whether TK levels in primary breast tumors can be used to predict recurrence and to establish the relationship between TK levels and estrogen receptor (ER) status and recurrence. Methods: Eighty-six patients with breast cancer were entered in this study. Tumors were assessed for ER status and TK levels, and the patients had follow-up for recurrence over a period of 41 months. By calculating the percent of TK activity in the presence of adenosine triphosphate (ATP) or cytidine triphosphate (CTP), we estimated the relative contributions of TK isozymes TK1 and TK2 to total TK activity. Results: Total TK (TK1 plus TK2) levels in tumors were significantly (P

Background. Early detection of local recurrence after conservative therapy for breast cancer is associated with improved survival. This review was undertaken to determine the ability to detect recurrence and identify patterns of recurrence. Methods. Records of women with local tumor recurrence were retrospectively reviewed. Results. In 42 women with 43 local recurrences, tumors were detected by mammography alone in 18 instances (42), physical examination alone in 14 (33%), and by both in 11 (25%). Of 29 recurrences mammographically detected, 19 were diagnosed by microcalcifications, 9 by a mass and 1 by a mass with microcalcifications. Twenty of 25 tumors detected by physical examination were felt as a mass. Recurrences detected by mammography were more often in situ (72% or 13 of 18) than those detected by physical examination alone (7% or 1 of 14. Treatment failure at the site of the original tumor seemed to occur earlier than failures elsewhere in the breast and was more common in women younger than 43 years of age or with disease that was originally axillary node-positive. Conclusions. Mammography often detects more in situ recurrences than physical examination, but both are complimentary. Recurrence at the site of the original tumor is usually earlier and in younger women and may be associated with tumors that were originally node-positive. Cancer 1992; 70:493-496.

Background. Four hundred thirty-three patients with recurrent breast cancer were treated by the authors at a large medical breast oncology facility from 1976-1982. The median survival time from first relapse (MSFR) for the 193 patients whose survival experience was not confounded by lead-time bias was 26 months. This MSFR is similar to that of most series published in the 1970s and 1980s and is approximately double that of series published in the 1960s. Methods. In this series, regression analysis identified disease-free interval (DFI), estrogen receptor (ER) status, and dominant disease site as significant prognostic variables, similar to other published series. Results. In 113 patients with known ER values, DFI, and dominant metastatic sites, a prognostic spectrum of MSFR patterns was identified among combinations of these three variables. The MSFR ranged from 15 months for poor risk patients with negative ER values, visceral dominant sites, and DFI of less than 24 months, to more than 90 months for good risk patients with positive ER values, soft tissue dominant sites, and DFI of more than 24 months. Although menopausal status alone was not a significant prognostic variable in regression analysis, 66% of premenopausal patients had a constellation of 'poor' prognostic variables. Conclusions. This type of prognostic factor analysis at first relapse could help identify subsets of patients who might be considered for aggressive investigational therapies such as high-dose chemotherapy with autologous bone marrow reconstitution. Cancer 1992; 70:129-135.

Fear of recurrence has been at the heart of the controversy between surgeons favoring mastectomy versus those advocating a less radical operation. Breast-conserving surgery is thought to result in a better body image, but patients are expected to worry more about a cancer recurrence because only a small part of the breast is exercised. To assess survival rates after breast-conserving intervention, patients were randomized into the National Surgical Adjuvant Breast Project (NSABP) prospective clinical trial (Protocol B06) with three treatment groups: total mastectomy, lumpectomy, and lumpectomy followed by radiation therapy. A fourth group was created to include patients who had a recurrence after their first operation and thus underwent a subsequent total mastectomy. Differences appeared, not according to the type of treatment, but with respect to the number of surgical interventions. Patients will multiple operations reported a greater fear of cancer recurrence and a worse body image, similar to those that underwent total mastectomy. Contrary to the trade-off hypothesis, patients who underwent radical surgery did not manifest less fear of recurrence. These results show unequivocally that the expected trade-off between breast conservation and fear of cancer recurrence does not occur. Those who undergo lumpectomy do not more express more fear of cancer than do patients who undergo mastectomy. Cancer 1992; 69:2111-2115.

One hundred twenty consecutive patients who had breast-conserving surgery for cancer and were referred for definitive radiation therapy (RT) had a mammogram performed before starting RT. This was done to determine the presence of residual neoplasm or other abnormalities that may alter or delay the planned RT and are undetected by other means. It also was performed to provide a baseline for the diagnosis of postoperative changes and recurrence of disease on follow-up studies. In six (5%) patients, calcifications or masses were found that proved to be residual tumors. This led to reexcision in two, mastectomies in two, and a higher radiation booster dose to the tumor bed in two. Eight (6.6%) patients had postoperative hematomas larger than 4 cm in diameter, which delayed the start of RT by 2 to 3 weeks. In 39 (32%) patients, the pre-RT mammogram provided information considered to be helpful for the interpretation of post-RT mammograms. Such information may lead to a decrease in the number of diagnostic biopsies based on indeterminate mammographic findings. Therefore, a routine mammogram is recommended before RT is started. Cancer 1992; 69:1418-1423.

Early breast cancer may be successfully treated by conservative surgery followed by radiation therapy. However, the amount of breast tissue that should be removed has not been determined. Some studies have suggested that increasing the area of the tissue removed may reduce the risk of cancer recurrence; however, this may not result in as good a cosmetic outcome as the removal of less tissue. A study was undertaken to determine the relationship between the volume of resected breast tissue and the likelihood of recurrence of the tumor within five years. The study included 507 patients with infiltrating ductal cancer of the breast who underwent conservative surgery and radiation therapy between 1968 and 1982. Patients were grouped by cancer stage (I or II), and within each stage patients were stratified by size of excised tissue and divided into three groups. Follow-up periods ranged from 17 to 219 months, with half the patients followed for 100 months or more. Actuarial survival was analyzed by tumor stage and the presence or absence of an extensive intraductal component. Extensive intraductal component refers to the simultaneous presence of cancer extending beyond the tumor margin; additional cancer in adjacent breast tissue that appears normal; or a tumor that is predominantly noninvasive, but with focal areas of invasion. Patients with a positive extensive intraductal component who had the largest amount of tumor removed had a substantially lower risk of recurrence than those who had the smallest amount of tissue removed (10 percent versus 29 percent for stage I cancer patients). The amount of tissue removed did not influence the outcome of patients without an extensive intraductal extension. These patients had lower recurrence rates than patients with positive intraductal extension. It is concluded that although small resection is adequate for patients without extensive intraductal component, those with an extensive intraductal component should have larger amounts of breast tissue removed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Conservative surgery has become more common in the treatment of breast cancer. While previously radical mastectomy was the standard treatment in virtually all cases, it has become common, particularly in women with very small tumors, to excise the primary lesion and remove the lymph nodes from the armpit (axilla), but to conserve most of the breast tissue. Usually, the affected breast is irradiated to help prevent the growth of any small remaining foci of tumor cells. However, irradiation was instituted as a cautionary measure, and it is uncertain that radiotherapy is actually necessary or provides any benefit. The authors reviewed the cases of 122 women with breast cancer who underwent conservative surgery without receiving radiation treatment to determine if omitting this treatment had adverse consequences. All the patients had invasive breast cancer that was treated with wide excision and the removal of the axillary lymph nodes. During the follow-up period, which varied from one to eight years, 22 patients had breast cancer recurrences and one had a recurrence of tumor in the armpit. When the researchers looked for factors which correlated with recurrence, they found that none of the 20 patients whose primary tumors were smaller than 1 centimeter suffered relapse. The likelihood of relapse seemed to be directly dependent upon the size of the primary tumor before surgery. The presence or absence of tumor cells in the lymph nodes of the armpit seemed to have no influence on relapse. Furthermore, it was observed that the likelihood of relapse was dependent upon age, as well. In the group of 122 women, 31 were over 70 years of age, and only one relapse was observed among these elderly women. The results of this study indicate that for some women, irradiation is an important aspect of treatment for breast cancer. However, for women with primary tumors smaller than one centimeter, and for patients over the age of 70, preventative irradiation may serve little purpose and the patient may no need this treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

It has been well established that for women with early breast cancers of the appropriate characteristics, conservative surgery in combination with radiotherapy is as effective as mastectomy. However, numerous questions remain to be answered and many research studies are currently in progress. As might be expected, key questions involve factors that influence the risk of local recurrence of the breast cancer. The histological appearance of the cancer affects the risk of recurrence. For example, when intraductal carcinoma cells are found in grossly normal tissue outside the margin of tumor invasion, the risk of recurrence is 25 percent, in contrast to the 5 percent risk overall. Young age is also thought to be an important risk factor, with a recurrence rate of well over 50 percent among patients under 35. Since younger patients usually have riskier histological findings, it might be thought that this alone accounts for the increased risk of younger patients. However, even when the histological findings of the tumor are accounted for, age under 35 carries an increased risk of recurrence. It is well established that conservative surgery alone is far riskier for recurrence than conservative surgery with radiotherapy of the breast. All patients receiving conservative surgery may be considered to be at high risk for recurrence. Curiously, however, it is not at all clear that local recurrence has a statistically significant effect on mortality in these patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research has shown that treatment of early breast cancer (stage I or II) with conservative surgery and radiation therapy is as effective as total mastectomy for achieving local control and improving survival. It also has the added cosmetic advantage of preserving much of the breast. Further surgery can be performed if this mode of treatment fails. However, early detection of such failure is crucial. This study looks at the role mammography (breast X-ray) plays in follow-up of patients who undergo conservative surgery and radiation therapy to treat breast cancer. Mammograms and clinical records were reviewed of 48 women who had undergone this treatment and who were later thought to have recurrence of cancer and underwent further biopsies. Twenty-four of these patients had recurrent cancer confirmed by biopsy. Twenty-three of the 24 recurrences were directly related to the initial disease. Mammograms had been obtained in 22 of the 24 patients within four months of diagnosis of the recurrence. New masses were seen in 5 of the 24 patients. Physical examination of the 24 patients resulted in 17 positive findings. Mammograms were positive in the seven patients with negative physical examinations and physical examinations were positive in nine of the cases in which mammograms were negative. Both were positive for eight of the patients. This indicates a complementary nature of the two exam modes. Malignant breast cancer turned up less frequently in the patients who were positive only on mammography than in those only positive on physical examination. These results indicate both mammography and physical examination are important in detecting recurrence of breast cancer. The optimal frequency of mammography is not clear, but once every six months is presently recommended. (Consumer Summary produced by Reliance Medical Information, Inc.)

Since the risk of developing a second breast cancer is high among breast cancer patients, most patients now receive adjuvant therapy in addition to breast surgery. This adjuvant therapy may take the form of chemotherapy, radiotherapy, or a combination of the two. Since the number of treated women is quite high, it becomes important to determine the long-term risks associated with adjuvant therapy. Since any cancer-causing effects of adjuvant therapy may take a decade or more to express themselves, only a long-term study involving a relatively large number of patients can provide answers to these questions. Such a study was conducted on 1,081 women, who were treated for primary breast cancer between 1970 and 1981. No patients included in the study had signs of distant cancer spread at the time of treatment. Of the 1,081 patients, 407 received only surgical treatment, 226 received adjuvant chemotherapy, 140 received adjuvant radiotherapy, and 308 received a combination of radiotherapy and chemotherapy in addition to surgery. Consistent with previous reports, the rate of new breast cancer developing in the other breast was elevated for all patients, but was highest among the patients who received only surgical treatment. There was no apparent elevation in the rate of solid nonbreast tumors developing in the patients, regardless of treatment. The rate of development of leukemia, however, was elevated among patients receiving surgery only, chemotherapy only, or chemotherapy in combination with radiotherapy. It should be emphasized that this elevation represents a total of four cases of leukemia in the patient population of 1,081, and the elevation was statistically significant for only the surgery group. The overall findings suggest that there is little or no negative impact of adjuvant therapy for breast cancer patients. Adjuvant chemotherapy and chemotherapy with radiation therapy appear to reduce the risk of breast cancer in the contralateral breast. (Consumer Summary produced by Reliance Medical Information, Inc.)

The early diagnosis of breast cancer has resulted in many women being treated with breast-conserving surgery. However, it is critical that appropriate follow-up be maintained, as these patients are at very high risk for recurrence. To help characterize the patterns of recurrence, information from 145 breast biopsies performed on 139 breasts was analyzed. Overall, 52 percent of the biopsies were positive. Among patients with a positive mammogram but with no physical signs, the positive biopsy rate was 66 percent. For patients with physical signs, such as a palpable mass, but a negative mammogram, the positive biopsy rate was 28 percent. For patients with both physical signs and mammographic evidence, 72 percent of the biopsies were positive. Complications from the biopsy procedure occurred in seven of 81 patients; the remaining patients could not be evaluated for complications due to subsequent mastectomy. Aspiration biopsies were found to have a significantly smaller rate of positive findings, but this is to be expected since aspiration biopsies are usually reserved for lesions with a low suspicion of cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Carcinoma of the breast is a disease that is associated with 10-year recurrence rates of 25% in operable patients with no spread to the axillary nodes and 75% in patients in whom the tumor has extended to the axillary nodes. Locoregional recurrence rates of close to 50% have been reported in patients with Stage III disease. Adjuvant prophylactic postoperative irradiation can reduce locoregional recurrences to less than 10%. When locoregional recurrence occurs after mastectomy, therapeutic irradiation is required. It can achieve tumor control in at least 50% of cases. The best conditions exist when a surgical procedure can achieve gross removal of the recurrent tumor before irradiation and when the fields of irradiation encompass the chest wall and pertinent lymph node areas. The required dose of radiation is lower after excision of the tumor, and the chances of local tumor control are higher. The dose of radiation must be 4500-5000 cGY (fractions of 180-200 cGY) to the subclinical disease and a boost of 1000-1500 cGY added to the known tumor areas. Distant metastatic manifestations must be dealt with for palliative purposes, except in the case of isolated supraclavicular metastasis, where radical irradiation can achieve cure. The need exists for a definition of the role of systemic therapy for locoregional recurrence, and for the development of the optimal integration of systemic chemotherapy and local radiotherapy in patients with locoregional or distant breast cancer recurrences.