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0360-3016/92 $5.00 + .oO 0 1992 Pergamon Press Ltd.

0 Clinical Original Contribution MICROINVASIVE DUCTAL CARCINOMA OF THE BREAST TREATED WITH BREAST-CONSERVING SURGERY AND DEFINITIVE IRRADIATION LAWRENCE J. SOLIN, M.D.,’ BARBARA L. FOWBLE, M.D.,’ I-TIEN YEH, M.D.,2 MICHAEL J. KOWALYSHYN, M.D.,3 DELRAY J. SCHULTZ, M.A.,4 MARISA C. WEISS, M.D.’ AND ROBERT L. GOODMAN, M.D.’ ‘Department of Radiation Oncology, University of Pennsylvania School of Medicine and the Fox Chase Cancer Center, Philadelphia, PA; ‘Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA; 3Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA; and 4Biostatistics Unit, University of Pennsylvania Cancer Center, Philadelphia, PA An analysis was performed of 39 consecutive women with microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation during the period 1977 to 1988. Microinvasive ductal carcinoma was defhmd as predominantly intraductal carcinoma with microscopic or early invasion. Surgical treatment of the primary tumor included excisional biopsy or wide resection. Axillary lymph node staging showed that 37 patients were pathologically node negative and two patients were pathologically node positive, each with only one positive lymph node. The median follow-up was 55 months (mean = 65 months; range = 25-135 months). The Syear actuarial rate of overall and cause-specific survival were both 97%. The 5-year actuarial rate of freedom from distant metastases was 93%. Nine patients developed a recurrence in the breast; eight of the nine patients had isolated local only first failures, and one of the nine patients had a local recurrence simultaneously with distant metastases. The median time to local failure was 42 months (mean = 53 months; range = 20-116 months). Of the eight patients with local only first failure, seven patients have been salvaged with further treatment and remain free of disease at the time of last follow-up, and one patient has died of subsequent distant metastatic disease. Median follow-up after salvage treatment was 29 months (mean = 27 months; range = O-54 months). Comparison of the patients with microinvasive ductal carcinoma with two control groups of intraductal carcinoma and invasive ductal carcinoma was performed. Although the rate of local failure was significantly higher for patients with microinvasive ductal carcinoma as compared to the two control groups, the rates of survival and freedom from distant metastases for patients with microinvasive ductal carcinoma were intermediate to the two control groups. Because of the high rates of survival and freedom from distant metastases and because of the ability to salvage patients with local recurrence, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast. Breast-conservation treatment, Radiation therapy, Microinvasion, Carcinoma of the breast. INTRODUCI’ION

serving surgery and definitive irradiation for patients with ductal carcinoma in situ (3, 5,6,7,25,29, 33, 38, 39,40,

42). Although the results of breast-conserving surgery and definitive irradiation for patients with ductal carcinoma in situ and for patients with invasive carcinoma have been evaluated in numerous studies, the outcome of such

Definitive irradiation following breast-conserving surgery is a well-established treatment alternative to conventional mastectomy for appropriately selected and staged patients with invasive carcinoma of the breast. The recent emphasis on screening mammography has increased the detection of earlier lesions including non-invasive, intraductal carcinoma (ductal carcinoma in situ) and early in-

treatment for patients with microinvasive ductal carcinoma of the breast is not well established. The current study was undertaken to evaluate in detail the results of definitive irradiation following breast-conserving surgery for patients with microinvasive ductal carcinoma of the breast treated at the Hospital of the Uni-

vasive carcinoma, and the referral of patients with such lesions for breast conservation treatment is increasing (36). Recent studies have reported the results of breast-con-

Radiation Oncology, Fox Chase Cancer Center, 770 1 Burholme Ave., Philadelphia, PA 19 111. Accepted for publication 9 March 1992.

Presented in part at the 33rd Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Washington, DC, 4-8 November 199 1. Reprint requests to: Lawrence J. Solin, M.D., Department of 961

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1. J. Radiation Oncology 0 Biology 0 Physics

versity of Pennsylvania and the Fox Chase Cancer Center. Previous studies have reported on the outcome of breastconserving surgery and definitive irradiation for invasive carcinoma (8, 34) and intraductal carcinoma (7, 38). METHODS AND MATERIALS An analysis was performed of 39 consecutive women who presented with unilateral microinvasive ductal carcinoma of the breast and were treated with breast-conserving surgery and definitive breast irradiation at the Hospital of the University of Pennsylvania and the Fox Chase Cancer Center. All patients were treated during the period 1977 to 1988. All patients were AJC (American Joint Committee) clinical Stage I (Tl NO MO) or II (T2 NO MO, Tl N 1 MO, or T2 Nl MO) ( 1). The criteria for selection of potential candidates for breast-conservation treatment with definitive breast irradiation have previously been described (4,8,34). Patients with bilateral carcinoma of the breast treated with bilateral breast-conserving surgery and definitive irradiation have previously been reported (35). Of the 39 patients, 15 patients (38%) were premenopausal, 21 patients (54%) were postmenopausal, and 3 patients (8%) were perimenopausal. The median patient age was 52 years (mean = 5 1 years; range = 28-75 years). For all patients, the surgical treatment included complete gross removal of the primary tumor with an excisional biopsy or wide resection, and pathologic axillary lymph node staging was performed for all patients. A reexcisional biopsy had been performed in 62% (24/39) of the patients. Pathologic axillary lymph node staging was performed in general using a lower axillary lymph node dissection of level I or levels I-II. Of the 39 patients, 37 (95%) were pathologically node negative, and two patients (5%) were pathologically node positive, each with only one positive axillary lymph node. The radiation treatments in all patients initially included breast tangential fields of 4400-5000 cGy using daily fractions of 180-200 cGy per fraction. A breast boost was delivered using either iridium implants or electrons of varying energy after the tangential fields. All patients except one received a total dose of 2 6000 cGy. The median total dose was 6000 cGy (range = 5940-6850 cGy). Three patients (8%) received radiation treatment to the supraclavicular region. Adjuvant systemic chemotherapy of cytoxan, methotrexate, and 5-fluorouracil was given to three patients (8%). Adjuvant hormonal therapy was not used in any of the patients. The median follow-up for all patients was 55 months (mean = 65 months; range = 25-l 35 months). For surviving patients only, the median follow-up was also 55 months (mean = 64 months; range = 25-135 months). The Kaplan-Meier method was used to calculate curves for survival, local control, and regional control ( 15). The time period was calculated as beginning at the start of definitive radiation therapy, not at the time of diagnosis

Volume 23, Number 5, I992

of carcinoma. Comparison of curves was performed using the Mantel-Cox test ( 18). For analysis of overall survival, patients were required to be alive at the time of last follow-up not to be considered as a failure. For analysis of NED (no evidence of disease) survival, patients were required to be alive and without evidence of disease at the time of last follow-up not to be considered as a failure. Therefore, a patient who had been salvaged following an isolated local failure with further treatment was not scored as a failure for NED survival. For analysis of cause-specific survival, a failure was scored only for a patient with a death from breast carcinoma. For analysis of freedom from distant metastases, the patient was scored as a failure at the time of first evidence of metastatic disease. A local failure was scored for a failure within the treated breast. A regional failure was scored for a failure which occurred in the ipsilateral axillary, infraclavicular, supraclavicular, or internal mammary nodal regions. “Local only first failure” was scored for a failure which occurred in the treated breast as the first and only site of failure without regional failure and without distant failure. “Regional only first failure” was scored for a failure which occurred in the regional nodal area(s) as the first and only site(s) of failure without local failure and without distant failure. “Local and regional only first failure” was scored for a failure which occurred simultaneously in the breast and regional nodal areas as the first and only sites of failure without distant failure. “First failure with any local component” was scored for a failure which included local failure with or without regional and/or distant failure at the time of first evidence of failure. Microinvasive ductal carcinoma was defined as predominantly intraductal carcinoma with microscopic or early invasion. The criteria for inclusion into the present study was either maximal extent of invasion of I 2 mm or invasive carcinoma comprising < 10% of the tumor. Small, purely invasive carcinomas were not included in the present study. The pathology slides were available for retrospective review in 27 of the 39 cases. All available microscopic slides were reviewed to confirm the diagnosis of microinvasive ductal carcinoma (22). The pathology slides were reviewed concurrently by two pathologists (I.-T.Y. and M.J.K.) without knowledge of the clinical outcome. Cases were not included in the present study if unequivocal invasion could not be demonstrated in the available pathologic material as judged by two pathologists (I.-T.Y. and M.J.K.). Invasion was defined as present if malignant cells were definitely outside the basement membrane of the duct or lobule on light microscopic examination. The invasive foci were typically irregular in size and shape, and stromal desmoplastic response adjacent to invasive foci was noted. The depth of invasion from the basement membrane, the maximal diameter of the invasive component, and the number of invasive foci were recorded. The histologic subtype of the non-invasive ductal component of the tumor was classified as comedo,

Microinvasive carcinoma 0 L. J.

cribriform, papillary, micropapillary, solid, or solid with focal necrosis (22). The nuclear grades of the intraductal component and the invasive ductal component were separately scored. Grade I was scored if the nuclei were relatively uniform with fine chromatin. Grade III was scored if the nuclei were pleomorphic with coarse chromatin clumping. Grade II was scored if the features were intermediate between Grade I and Grade III. The final pathology margin was determined from review of the pathology reports in the patient records (37). The final pathology margin was scored from the re-excisional biopsy, if performed, or from the initial excisional biopsy, if a re-excisional biopsy had not been performed. The final pathology margin was scored as negative when all tumor identified was greater than 2 mm from the inked margin ofthe tumor excision or when no tumor was identified within the re-excisional biopsy specimen. The final pathology margin was scored as positive when any tumor was identified at the inked margin of the tumor excision. The final pathology margin was scored as close when tumor was identified I 2 mm from, but not at, the inked margin of the tumor excision. Patients with positive or close margins were focally microscopically positive or close, respectively (37). Two control groups were defined for comparison with the patients with microinvasive ductal carcinoma of the breast. The two control groups consisted of similarly treated patients with non-invasive, intraductal carcinoma (ductal carcinoma in situ) of the breast and invasive ductal carcinoma of the breast, respectively. Because of the strong prognostic importance of pathologic axillary nodal staging and because 95% (37/39) of the patients with microinvasive ductal carcinoma were pathologically node negative, patients with invasive ductal carcinoma were required to be pathologically node negative, and patients with intraductal carcinoma of the breast were required to be pathologically node negative, if pathologic nodal staging was performed, or clinically node negative, if pathologic nodal staging was not performed. These two control groups were then compared to the pathologically node negative patients with microinvasive ductal carcinoma of the breast. The two control groups were treated similarly during the same time period. Comparison of the microinvasive ductal carcinoma cases with the two control groups was performed in two ways. First, the follow-up times were adjusted to be similar for the three groups, although this resulted in slightly different dates of treatment for the patients with intraductal carcinoma (January, 1977-June, 1988) in comparison to the patients with microinvasive ductal carcinoma or with invasive ductal carcinoma (both January, 1977-December, 1988). Second, identical dates of treatment (January, 1977-December, 1988) were used for all three groups, although this resulted in slightly different median follow-up times for the three groups. As the results for both sets of analyses were virtually identical, the data reported (see Results) are from only the first of the two analyses.

SOLIN et al.

963

RESULTS The clinical presentation for the 39 cases is shown in Table 1. Of the 39 patients, 18 presented with mammographic findings only, 19 presented with a mass on physical examination with or without mammographic findings, and 2 had other presentations. The tumor characteristics for the 39 lesions are shown in Table 2. Clinical staging showed that 72% (28/39) of the cases were Tl lesions, and 28% (1 l/39) of the cases were T2 lesions. Review of the final pathology margins from the patient records showed that 44% (17/39) of the cases were unknown, and this reflects that routine inking of surgical biopsy specimens was not commonly performed during the earlier years of the study. Of the 22 cases for which the final pathology margin was evaluable, 86% (19/22) were negative. The site(s) of first failure are shown in Table 3. There were nine total patients with local failure. No regional nodal failures were detected during the course of followup for any of the 39 patients. The actuarially calculated outcomes for survival, local control, and regional control at five years are shown in Table 4. Figure 1 shows the curve for overall survival and cause-specific survival. Figure 2 shows the curve for freedom from distant metastases. Figure 3 shows the curves for local control. For the nine patients with local failure, the median time to failure was 42 months (mean = 53 months; range = 20- 116 months). The incidence of local failure was lower for cases in which the final pathology margin of the primary tumor excision was negative ( 1/19; 5%) as compared to cases in which the final pathology margin from the primary tumor excision was unknown (6/17; 35%), positive (l/2), or close (l/l). In 27 of the 39 cases, the pathology slides were available for retrospective review. The pathologic findings for the 27 evaluable cases are shown in Table 5. The pathologic characteristics of the primary tumors were known for 6 of the 9 cases which subsequently developed local failure,

Table 1. Clinical presentation Number Mammographic findings only Microcalcifications Mass

Mass and microcalcifications Mass on physical examination only Mass on physical examination plus mammographic findings Microcalcifications Mass Mass and microcalcifications Other Total * Includes grams.

two patients

with negative

12 4

2 8* 2 6 3 2 39 post-biopsy

Percent 31 10

5 21 5 15 8

5 100 mamma-

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Table 2. Tumor characteristics

Clinical tumor size 5 2.0 cm 2. I-3.0 cm 3. I-5.0 cm Unknown Clinical T stage Tl T2 Pathologic N stage Node negative Node positive 1 positive lymph node > 2 positive lymph nodes Final pathology margin Negative Positive Close (5 2 mm) Unknown Estrogen receptor status Negative Positive Not done/unknown Progesterone receptor status Negative Positive Not done/unknown

Table 4. Actuarial outcome data

Number

Percent

13 5 3 18

33 13 8 46

28 I1

72 28

37

95

Percent at 5 years Survival Overall NED (no evidence of disease) Cause-specific Freedom from distant metastases First failure Local only Regional only Local and regional only First failure with any local component

97 93 97 93 18 0 0 20

5

2 -

-

19 2 1 17

49 5 3 44

2 13 24

5 33 62

6 8 25

15 21 64

and the pathologic characteristics for these 6 cases were generally unfavorable. In 5 of the 6 cases, the histologic

subtype of the intraductal carcinoma component was comedo carcinoma, the nuclear grade of the intraductal carcinoma component was grade III, and the nuclear grade of the invasive ductal carcinoma component was grade III. In 1 of the 6 cases, the histologic subtype of the intraductal carcinoma component was cribriform carcinoma, the nuclear grade of the intraductal carcinoma component was grade I, and the nuclear grade of the invasive ductal carcinoma component was grade I. All eight of the potentially salvageable patients with local only first failure (Table 3) were initially rendered free of disease with salvage mastectomy, and two of the eight patients were also treated post-mastectomy with systemic chemotherapy. Of the eight patients with local only first failure, seven patients have remained free of

disease at the time of last follow-up, and one patient subsequently developed distant metastatic disease and died. The median follow-up after salvage treatment for the eight patients with local only first failure was 29 months (mean = 27 months; range = O-54 months). For the eight patients with local only first failure, the location of the recurrence within the treated breast showed that six cases were infield or marginal and two cases were elsewhere (26). The pathology at the time of recurrence showed that six of the recurrences were invasive ductal carcinoma, and two of the recurrences were non-invasive, intraductal carcinoma. Table 6 shows a comparison of patients with microinvasive ductal carcinoma with two control groups of patients with non-invasive, intraductal carcinoma (ductal carcinoma in situ) and invasive ductal carcinoma. The rate of local failure was higher for patients with microinvasive ductal carcinoma as compared to the two control

-

97%

Table 3. Site(s) of first failure Site(s) of first failure None Local only Regional only Distant only Local and regional Local and distant Local, regional, and distant Total

Number 30 8 1 39

Percent 77 21 3 100

NUMBER AT RISK 39 0

39

39

1

2

33

28

17

3

4

5

YEARS Fig. 1. Overall survival and cause-specific survival. The curves for overall survival and cause-specific survival are identical through 5 years of follow-up. The number at risk represents the number of patients at risk by year intervals.

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Microinvasive carcinoma 0 L. J. SOLIN et al. Table 5. Pathologic findings for the 27 evaluable cases

Number

Percent

18 3 2 2 2 -

67 11 7 7 7 -

2 8 17

7 30 63

1 8 18

4 30 67

17 6 4

63 22 15

Histologic subtype of the intraductal carcinoma component

25 NUMBER AT RISK 39 OO

39

39

1

2

32

28

18

3

4

5

YEARS Fig. 2. Freedom from distant metastases. The number at nsk

represents the number of patients at risk by year intervals.

groups of patients with intraductal carcinoma and invasive ductal carcinoma. Analysis of survival outcomes showed that the survival of patients with microinvasive ductal carcinoma was intermediate to the two control groups of patients. Comparison of the microinvasive ductal carcinoma patients with the two control groups of patients with non-invasive, intraductal carcinoma and invasive carcinoma showed no difference for patient age (I 35 years vs 36-50 years vs 2 51 years), the final pathology margin from the primary tumor excision, or the use of adjuvant systemic hormonal treatment (all p 2 .15 using

Comedo Cribriform Papillary Micropapillary Solid Solid with focal necrosis Nuclear grade of the intraductal carcinoma component Grade I Grade II Grade III Nuclear grade of the invasive carcinoma component Grade I Grade II Grade III Maximum depth of invasion < 1 mm l-2 mm Unknown

the chi-square test). There were differences (chi-square test) amongst the three groups (microinvasive vs. noninvasive vs. invasive ductal carcinoma) for the use of reexcision (65% vs 42% vs 46%, respectively; p = .054),

clinical tumor size I 2.0 cm (for patients only with known clinical tumor size, 63% vs 81% vs 56%, respectively; p = .008), use of systemic chemotherapy (3% vs 0% vs 7%, respectively; p = .Ol), total dose 2 6000 cGy (97% vs 83% vs 94%, respectively; p = .0002), ER status (p < .OOOl), and PR status (Q < .OOOl).

NUMBER AT RISK 5y

3p

38

2.9

2.4

FIRST FAILURE WITH ANY

,

1

,

1p

,

c-.-2o%

,LYIyJ;;E8%,

2

3

4

5

YEARS Fig. 3. Local failure. The number at risk represents the number of treated breasts at risk by year intervals.

DISCUSSION

The present study has reported the outcome of patients treated with breast-conserving surgery and definitive irradiation for microinvasive ductal carcinoma of the breast. The 5-year actuarial rate of overall survival and causespecific survival were both 97%. The 5-year actuarial rate of freedom from distant metastases was 93%. Of the eight patients with local only first failure (Table 3), seven were salvaged with further treatment, and one developed subsequent distant metastases and died. However, follow-up after salvage treatment was short (median = 29 months; range = O-54 months). The rates of survival and freedom from distant metastases were high because of the ability to detect and treat local recurrence. For the nine cases which subsequently developed local failure, the pathologic characteristics of the primary tumors were generally unfavorable. The incidence of local recurrence was lower for cases in which the final pathology margin from the primary tumor excision was negative ( l/ 19; 5%) as compared to unknown (6/ 17; 35%), positive

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Volume 23, Number 5. 1992

Table 6. Comparison of microinvasive ductal carcinoma with intraductal carcinoma (ductal carcinoma in situ) and invasive ductal carcinoma Non-invasive intraductal carcinoma*

Microinvasive ductal carcinoma+

Invasive ductal carcinoma+

102 l/77-6188

37 l/77-12/88

661 l/77-12/88

Number of patients Dates of treatment Follow-up (months) Median Mean Range Five-year actuarial survival Overall NED (no evidence of disease) Cause-specific Five-year actuarial freedom from distant metastases Five-year actuarial local failure Local only first failure First failure with any local component

P value*

56 61 2-152

55 62 25-135

54 59 2-161

99% 97% 100% 98%

96% 92% 96% 92%

92% 85% 93% 86%

.I0 .002 .04 .0007

2% 2%

19% 22%

6% 7%

.006 .002

* Clinically or pathologically axillary lymph node negative. + Pathologically axillary lymph node negative. t Mantel-Cox test (18).

(l/2), or close (I/ 1). These findings suggest that the cases which subsequently developed local recurrence may have had more disease at presentation than was appreciated

clinically. The use of re-excisional biopsy and pathologic confirmation of negative margins of the primary tumor excision may be important to optimize local control. Therefore, better patient selection has the potential to improve the risk of local recurrence. However, it is difficult to draw firm conclusions given the small number of patients in the subgroups. The definition of microinvasive carcinoma is not well established in the literature. Rosner et al. (28) defined ductal carcinoma in situ (DCIS) with microinvasion as “DCIS with limited microscopic stromal invasion below the basement membrane in one or several ducts but not invading more than 10% of the surface of the histologic sections examined.” Schuh et al. (30) defined microin-

vasive carcinoma as DCIS with the presence of early stromal invasion. Patchefsky et al. (24) used a definition of “predominantly intraductal tumors showing either focal infiltration outside the basement membrane or stromal invasion that accounted for less than an estimated surface area of 10% in the sections examined.” Silverstein et al. (33) defined microinvasion as “ 1 or 2 minute microscopic foci of possible invasion no more than 1 mm in maximum diameter.” Wong et al. (4 1) defined microinvasive ductal carcinoma as intraductal carcinoma “with only a microscopic focus of malignant cells invading beyond the basement membrane of the duct as determined by light microscopy.” The incidence of pathologically positive axillary lymph node metastases for patients with microinvasive ductal carcinoma of the breast has been reported as 20% (6/30) by Schuh et al. (30) 10% (4/41) as reported by Kinne et

al. (16) 3% (l/35) as reported by Rosner et al. (28) 0%

(O/l 7) as reported by Patchefsky et al. (24), and 0% (O/33) as reported by Wong et al. (4 1). For the two patients in the present study with positive axillary lymph node metastases, each showed only one positive axillary lymph node. In the study of Rosner et al. (28), the one patient with positive axillary lymph nodes also had only a single positive axillary lymph node metastasis. For the six patients with positive axillary lymph node metastases in the report of Schuh et al. (30), the mean number of positive axillary lymph nodes was 4.4 with a range of l-9. In view of the incidence of axillary lymph node metastases, surgical axillary staging remains an important component of the overall treatment program for patients with microinvasive ductal carcinoma of the breast. The pathologic examination of microinvasive carcinomas in comparison to non-invasive, intraductal carcinomas shows that the microinvasive carcinomas are correlated with adverse prognostic features in comparison to the non-invasive, intraductal carcinomas. Lagios et al. ( 17) found that the incidence of occult microinvasion was strongly correlated with the maximum extent of the intraductal carcinoma and that occult microinvasion was seen only in tumors in which the maximum extent of the intraductal carcinoma was > 45 mm. Patchefsky et al. (23) reported that 57% (12/2 1) of patients with microinvasive carcinoma had comedo intraductal carcinoma, and 42% (5/12) of small comedo intraductal carcinomas involving < 50 ducts showed microinvasion. Silverstein et al. (33) found that comedo intraductal carcinomas were more commonly associated with microinvasion than other histologic subtypes of intraductal carcinoma. In a pathologic study of 190 mastectomy specimens, Matsukuma et al. ( 19) reported that lesions of intraductal carcinoma with invasive areas comprising < 20% of the tumor were found to be of low nuclear grade more frequently and to have

Microinvasive carcinoma 0 L. J. SOLIN etal.

a histologic pattern of intraductal carcinoma of comedo or solid carcinoma less frequently than either non-invasive, intraductal carcinomas or more extensive invasive ductal carcinomas. Schwartz et al. (3 1) found that the incidence of multicentricity on mastectomy was 50% (5/ 10) for patients with microinvasive carcinoma as compared with 47% ( 15/32) for in situ ductal carcinoma and 35% (40/ 113) for invasive ductal/lobular carcinoma. For patients with microinvasive ductal carcinoma, treatment historically has been with mastectomy, and the outcome of treatment with mastectomy has shown high rates of survival. Kinne et al. (16) reported that 39 of 42 patients treated most commonly with mastectomy were without evidence of disease at the time of last follow-up with a median follow-up of 11.5 years. Schuh et al. (30) reported that 23 of 30 patients treated with mastectomy were without relapse at last follow-up with a mean followup time of 5.5 years. Wong et al. (41) reported that 36 of 37 patients treated most commonly with mastectomy were without relapse at the time of last follow-up with a median follow-up of 47 months. In the report of Wong et al. (4 l), nine patients were treated with breast-conserving surgery and definitive radiation therapy, and none of the patients developed a local recurrence. In the present study, the 5year actuarial NED survival of 93% at 5 years is similar to the reported outcome of treatment with mastectomy. The term “minimal breast cancer” has been used in the literature to attempt to define patients with early lesions. However, the term minimal breast cancer should not be used interchangeably with microinvasive breast cancer as minimal breast cancer is commonly defined broadly to include both in situ lesions and lesions with significantly more invasion than microinvasive carcinoma. Although definitions of minimal breast cancer frequently include in situ carcinomas, the term minimal breast cancer also includes carcinomas with invasion up to 5 mm (9, 10, 13, 20, 21) or up to 1 cm (2, 14, 27, 32).

967

For patients treated with breast-conserving surgery and definitive irradiation, the presence of an extensive intraductal component (EIC) has been associated with an increased risk of local recurrence (11). Microinvasive ductal carcinomas comprise a subset of tumors which are classified as EIC positive as the definition of EIC positive tumors includes either (a) predominantly intraductal carcinomas with microinvasion or (b) tumors with intraductal carcinoma comprising 2 25% of the area of the infiltrating tumor as well as the presence of intraductal carcinoma in grossly normal adjacent breast tissue. The finding that EIC positive tumors are associated with an increased risk of local recurrence, but not distant failure, is similar to the findings in the present study (Table 4). Healy et al. (12) have reported that 83% (34/41) of EIC positive tumors demonstrated microcalcifications on preoperative mammography. In the present study of patients with microinvasive ductal carcinoma, 49% (19/39) of the cases were found to have microcalcifications identified on preoperative mammography (Table 1). In summary, the present study has demonstrated the outcome of breast-conserving surgery and definitive irradiation for patients with microinvasive ductal carcinoma of the breast. The 5-year actuarial rate of overall and cause-specific survival were both 97%, and the 5-year actuarial rate of freedom from distant metastases was 9 3%. Although the 5-year actuarial risk of local recurrence was 20%, 7 of 8 potentially salvageable patients with local only recurrence were salvaged with further treatment of mastectomy with or without systemic chemotherapy. Because of the ability to salvage patients with local recurrence, the rates of survival and freedom from distant metastases were high. Therefore, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast.

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