Breast Patricia
R. Hassell, W. Kingston,
Gary
MD MD
#{149} Ivo #{149} Vivien
Early Breast of Recurrence Surgery and
A. Olivotto, E. Basco,
Cancer: after Radiation
To determine the clinical and mammographic features of recurrent breast cancer after tumorectomy and radiation therapy, the authors reviewed the clinical history and serial mammograms of 48 patients with suspected recurrence. Of patients with recurrent disease, seven had positive mammograms alone, nine had positive findings at physical examination alone, and eight had both positive mammograms and positive results of physical examination. Positive mammographic findings included the development of new fine calcifications (six patients), a new mass (five patients), mass and calcifications (one patient), increasing opacity (two patients), or skin thickening (one patient). Patients in whom the breast recurrence was detected mammographically alone were less likely to develop metastatic disease in subsequent follow-up than when results of physical examination were positive at the time of breast recurrence. Serial mammographic and clinical examinations are complementary for optimal detection of recurrence after conservative surgery and radiation therapy. Index Breast
terms: Breast, calcification, neoplasms, diagnosis, 00.32
plasms,
postoperative,
plasms,
therapy,
00.45
00.81
#{149}
Breast neo-
neo-
#{149}
Breast
#{149}
MD MD
#{149} Helmut
MD
Detection Conservative Therapy’
C
ONSERVATIVE surgery followed by radiation therapy has become an accepted treatment for women with stage I and II breast cancer. Three modern, prospective, randomized trials with long-term follow-up demonstrated no adverse effect on rates of overall survival or local control when the efficacy of conservative surgery and radiation therapy
was
compared
with
that
of total
mas-
tectomy (1-3). The combination of conservative surgery and radiation therapy offers the additional advantage of preserving the breast, usually with a highly satisfactory cosmetic result (4-6). Local failure of treatment can still be salvaged by further surgery, with 63%-69% of patients remaining free of further local on distant disease at 5 years after a recurrence of operable cancer of the breast (7,8). Early detection of these treatment failures may improve salvage rates. The role of mammography in the follow-up of patients undergoing conservative surgery and radiation therapy is not well defined. This report describes our experience with 48 patients who had suspected recurrence of breast cancer after conservative surgery and radiation therapy for stage I or II breast cancer.
00.1299
PATIENTS Radiology
A. Mueller,
1990;
AND
METHODS
176:731-735
The
British Columbia Cancer Agency is a regional cancer treatment center that serves a population of more than 3 million. Since 1979, conservative (BCCA)
surgery
From the Divisions of Diagnostic Imaging (P.R.H., HAM.) and Radiation Oncology (LAO., V.E.B.), British Columbia Cancer Agency, 600 W 10th Aye, Vancouver, BC V5Z 4E6, Canada; and the Department of Surgery, University of British Columbia, Vancouver (lAO., G.W.K., V.E.B.). From the 1989 RSNA scientific I
assembly.
Received
requested
November
May
7, 1990;
requests C
RSNA,
accepted
to P.R.H. 1990
October
12, 1989;
13; final May
revision
21. Address
revision
received reprint
Imaging
and
radiation
therapy
have
been
used increasingly for women with stage I and II (Union Internationale Contre be Cancer) breast cancer. Surgery consisted of excision of the primary tumor with a 1 -2-cm margin of grossly normal tissue and an axillary node dissection. Radiation therapy consisted of a tangent pair to the breast; a tumor dose of 44 Gy was delivered in 16 fractions over 31/2 weeks. A boost with cobalt or 7-1 1-MeV electrons with a given dose of 5 Gy in two fractions
was added to the primary site in approximately one-third of patients, generally when the margins were close on involved on a microscopic level. The regional nodes received a tumor dose of 37.5 Gy in 16 fractions from a direct internal mammary field and opposed supraclavicularaxillary fields. Nodal irradiation was used in all patients who had involved nodes in the early years but selectively in patients with a high risk of recurrence, such as those with more than four involved nodes on those demonstrating extranodal extension of disease in the later years. After treatment was complete, patients were followed up by means of physical examination at the BCCA or in conjunclion with the referring surgeon at 3-6month intervals. Mammograms of the treated breast were obtained every 6 months for 3 years and yearly thereafter. The contralateral breast was examined mammographicabby once a year. Mammograms obtained at BCCA were solely xeromammograms until December 1987 and screen-film mammograms thereafter. Xenomammograms were available for neview in 28 patients, and screen-film mammograrns were available in 16 patients. Patients included in this study were drawn from two sources. Our institution maintains a data base of 348 consecutive women treated between 1979 and 1985. Forty-three
patients
who
underwent
open biopsy of the treated breast for suspected recurrence were identified and included. Twenty-one patients had malignant disease at biopsy, 21 had benign changes, and one patient had initial benign biopsy results and later developed another mass that biopsy results confirmed as a recurrent malignancy. We identified an additional five consecutive patients (two with malignancy and three with benign biopsy results) from the private practice of two authors (I.A.O., V.E.B.) in 1986 and 1987. Therefore, the study population includes 48 women who underwent 49 biopsies for suspected recurrence of cancer in the treated breast aften conservative surgery and radiation therapy.
Abbreviation: Cancer
BCAA
=
British
Columbia
Agency.
731
For this study, the clinical, surgical, and pathologic records were reviewed. All available mammograms, including those obtained prior to the original diagnosis, after treatment, and immediately prior to the biopsy for suspected recurrence, were obtained and reviewed independently and subsequently by two radiobogists (P.R.H., H.A.M.). Mammograms were considered suspect for recurrent disease if there was evidence of (a) new fine calcifications, (b) a new mass that deveboped in comparison with the baseline mammogram obtained 6 months after treatment, (c) an increase in architectural distortion or opacity of the breast parenchyma, or (d) an increase in the skin thickening after the posttreatment changes had subsided. All patients with further cancer anywhere in the treated breast were considered to have recurrence. The median age of the 48 patients at the time of diagnosis was 53 years, with a range of 22-84 years. The initial pathologic diagnosis was ductal carcinoma in 40 patients, lobular carcinoma in five patients, colboid carcinoma in two patients, and medullary carcinoma in one patient.
were proved to have recurrent cancinoma. Twenty-two recurrent cancers were confirmed by means of open biopsy and two at autopsy. Results of histologic examination of the recurrent cancers were identical to results of such examination of the original primary tumor in 23 of 24 patients (96%). Recurrences were related to the primary site in 21 of 24 patients (88%). Two patients had involvement of the entire breast, and one patient developed a new mass in a quadrant
different from that of the original carcinoma. Table 1 demonstrates the original indication for biopsy as described in the clinical chart. The results of approximately 50% of biopsies performed because of suspicion after mammography (seven of 13 biopsies) or clinical examination (14 of 29 biopsies) were positive. Clinical suspicion was based on the presence of a mass on new thickening in all instances. The one patient in Table 1 in
RESULTS The median time from diagnosis to subsequent biopsy for suspected recurrence was 24 months (range, 4-59 months). Patients with benign biopsy results tended to undergo biopsies in the earlier period of follow-up. The median time from diagnosis to benign findings at biopsy was 15 months (range, 4-53 months). The median time from diagnosis to biopsy that proved malignancy was 28 months (range, 6-59 months). A total of 23 of 25 patients with benign findings at biopsy were alive when last examined 3-102 months after biopsy, compared with 17 of 24 patients with biopsy-proved malignancy who were last examined 1-49 months after diagnosis of recurrence. Twenty-four of the 48 patients
a.
b.
(a) Mammogram obtained 1 1 months after treatment shows architectural hon and radiation-induced skin thickening. (b) Mammogram obtained 25 months ment shows the development of malignant calcifications posterior to the previous resection site. Note reduction in skin thickening. Results of biopsy demonstrated infiltrating ductal carcinoma. Figure
732
#{149} Radiology
1.
distorafter treatsegmental in situ and
September
1990
whom biopsy was indicated for en” reasons underwent mastectomy for sive
not
cosmetic breast suspected
clinicably at that time, but at mastectomy the patient was found to have extensive disease recurrence. Twenty-two of the 24 patients found to have recurrent breast malig-
“oth-
reasons due to progresfibrosis. Recurrence was mammognaphicalby on
nancy underwent mammography within 4 months prior to the diagnosis of that recurrence. On review, the mammographic findings were positive in 15 patients (68%) and negative in seven patients (32%) (Table 2). Five of the six patients who developed calcification as the sole manifestation of recurrent disease had infiltrating and in situ carcinoma, and one patient had in situ ductab carcinoma alone (Fig 1). These patients are all alive, of 35 months
b. Figure 2. (a) Posttreatment region. (b) Mammogram in the inferior hemisphere. carcinoma.
craniocaudal view shows postoperative changes in the areobar obtained 25 months later shows a mass 1.2 cm in diameter (arrow) Pathologic findings indicated the presence of a second primary
with a median (range, 21-61
follow-up months)
after recurrence and without evidence of local or distant metastatic disease. Mammograms revealed a new mass in five of the 24 patients. The results of concurrent physical examination were positive in four patients. Two of these have since died of metastatic disease, one is alive with lung metastasis, and one is alive and well. The one patient with negative results of physical examination had a mass 1.2 cm in diameter in a different quadrant and of different histologic charactenistics than the original primary tumor; this mass likely represents a new primary tumor but was scored as a recurrence for this report (Fig 2). One patient had a new mass and calcifications with negative results of physical examination. She is alive and well. The results of physical examination were positive in both patients with increasing architectural distontion and breast opacity. One patient died of metastatic disease, and one is alive without evidence of further bocal or distant metastases. One patient showed increased skin thickening only. This developed after the skin thickening associated with surgery and radiation therapy had subsided. She subsequently developed distant metastases and died (Fig 3). Seven patients had negative mammograms. The diagnosis was made on the basis of clinically increasing nodulanity on mass at physical examination. Three of these patients are alive without metastasis, two are alive with active disease, and two have died of metastatic disease. Two patients without prior mammograph-
I Figure months
b.
Volume
176
#{149} Number
3
3. after
(a) Mammogram treatment
obtained shows
minimal
18 re-
sidual treatment-induced skin thickening. (b) Mammogram obtained 19 months later shows the development of marked skin thickening and increased parenchymal breast opacity.
Radiology
#{149} 733
ic evaluation underwent an open opsy, the results of which confirmed recurrence. Both died of metastatic disease. Twenty-five patients underwent
bi-
biopsies the findings of which were benign. The pathologic findings of these biopsies included radiation fibrosis, hematoma, cysts, fibroadenoma, foreign body reaction, and fat necrosis. Six of these biopsies were prompted by the original nadiobogist’s concern about the mass and opacity at the primary site; four patients had abnormal mammograms and a suspect physical examination, and 15 patients underwent biopsy for clinical indications only with no radiobogic suspicion of abnormality. In 22 of these 25 patients, mammograms were obtained within 4 months of the biopsy. On review of serial posttneatment mammograms (Table 3), only two of 22 patients were classified as suspect for recurrent malignancy according to the cnitenia in this report. One of these patients had a well-defined mass 1 .6 cm in diameter with a central coarse calcification. The mass increased slightby to 1 .8 in diameter 1 1 months later, and biopsy findings confirmed the presence of a fibroadenoma. The othen false-positive mammogram was an initial posttneatment image that showed increased opacity in the area where surgery was performed; this opacity was due to scarring at biopsy. In nine additional patients, a mass or opacity at the primary site was identified on the first posttreatment “baseline” study. In this review, these mammographic changes were therefore not considered suspect, although in some cases the posttreatment changes had been of sufficient concern to prompt a recommendation for biopsy by a radiologist from another institution (Figs 4, 5).
to be maximal at 6 months and to stabilize or resolve with time. Although the findings of recurrent breast cancer may be similar to those seen as a result of surgery and radiation treatment, the pattern of change with time should suggest the diagnosis. Compression magnification views may increase the ability to define changes at the primary site. The reappearance of skin thickening, or an increase in breast opacity alone after the skin thickening due to surgery and radiation treatment has decreased, should be considered highly suspect for recurrent breast cancer (13,15), even in the absence of other findings. The benign changes seen in the region of the surgery include increased opacity, stellate masses, or both. These can be difficult to differentiate from residuab or recurrent disease. However, these findings should either stabilize or decrease with time if they are due to postoperative scarring, hematoma, or seroma (11,16). Also, the margins of hematomas or seromas tend to be well defined and the masses more homogeneous than in recurrent cancer. Hematomas can persist unchanged for years (12). The use of ultrasound and aspiration is extremely helpful in these patients and may make a repeat biopsy unnecessary. Obtaining a posttreatment mammogram within the first 6 months after radiation therapy will provide a baseline study at a time when it is unlikely that
recurrence will already be developing. Subsequent mammograms can then be compared with this baseline as a reference to the amount of surgical and radiation change within the treated breast. Because the mammographic findings of recurrent disease are often subtle, mammograms of the highest quality are essential and serial observations are vital to detect early changes. The site of recurrence in this series and as reported previously (1,9,10) was usually in the same quadrant as the segmental resection. This area must be optimably imaged. Because of distortion to the breast, optimal imaging may be difficult and may require additional views. Magnification views can be helpful and are recommended selectively in patients in whom new mammographic findings have developed.
DISCUSSION Serial clinical and mammographic follow-up is essential in the detection of recurrent breast cancer. The frequency of negative mammograms (seven of 22 patients) and the substantial proportion of recurrences not detected at dinical examination (seven of 24 patients) in this series have been reported previously (9,10) and emphasize the importance of complementary clinical and mammographic follow-up. The mammographic findings after segmental resection and radiation treatment include increased skin thickening and increased parenchymal opacity of the breast. These have been well described (11-14). Treatment changes tend 734
#{149} Radiology
a.
b.
Figure 4. (a) Mammogram obtained 16 months after segmental defined bobulated mass 5.0 cm in diameter in the area of surgery, ma or seroma. (b) The mass is slightly smaller on this mammogram,
resection shows a sharply consistent with a hematoobtained 4 months later.
September
1990
All six patients in this series who had new fine calcifications as an isolated abnormality had recurrent disease. Unlike patients in previous reports (9,10), five of the six patients had infiltrating ductal as well as in situ carcinoma, and only one patient had carcinoma in situ alone. The development of new coarse calcifications was not unusual and was not considered suggestive of malignancy. Of the patients in whom the diagnosis of recurrent cancer was made on the basis of mammographic findings alone, all did well subsequent to mammography, with no evidence of distant metastasis or death in seven patients 25-53 months after treatment of the recurrence. Patients whose recurrence appeared clinically, with or without positive mammograms, did poorly; 12 of 17 died of disease or were alive with distant metastases, reflecting a more mabignant course of disease. The optimal timing and frequency of follow-up mammography has not been established. Recht et ab (7) analyzed the time course of treatment failure after
conservative surgery and radiation therapy and showed that the risk of ipsibateral breast cancer recurrence peaks at a rate of 2.5% per year between 2 and 6 years after treatment. The risk of recurrent breast cancer then diminishes, but patients remain at risk even 10 years after treatment (8,10); many of the “recurrences” beyond 10 years may represent the development of a new primary cancer (8). Our policy of obtaining mammograms of the treated breast at 6-month intervals and mammograms of the opposite breast at 12-month intervals was established as part of an ongoing study to determine the optimal frequency of mammograms because recurrence in the breast can be treated for cure. We still have too few recurrences to assess optimal frequency. At present we continue to recommend physical examination at least once every 6 months, mammography of the treated breast at least once every 6 months, and mammography of the contralateral breast once a year. U
Acknowledgment: ret Buchwitz
AIMBI,
The authors and
Sarah
for assistance
1.
2.
3.
4.
5.
6.
Rose
MA, Olivotto
9.
11.
12.
13.
14.
15.
16.
B, et al.
Conser-
Recht A, Silen W, Schnitt SJ, et al. Timecourse of local recurrence following conservative surgery and radiation therapy for early stage breast cancer. Int J Radiat Oncol Biol Phys Kurtz second
1988; 15:255-261. JM, Amalric R, Delouche C, et al. The ten years: long term risks of breast
in early
Oncol
Biol
Phys
breast
cancer.
1987;
Int J Ra-
13:1327-1332.
Stomper PC, Recht A, Berenberg AL, et al. Mammographic detection of recurrent cancer in the
10.
IA, Cady
vative surgery and radiation therapy for early breast cancer: long-term cosmetic results. Arch Surg 1989; 124:153-157. Clarke D, Martinez A, Cox RS. Analysis of cosmetic results and complications in patients with stage I and II breast cancer treated by biopsy and irradiation. Int J Radiat Oncol Biol Phys 1983; 9:1807-1813. Ray GR, Fish VJ. Biopsy and definitive radiation therapy in stage I and II adenocarcinoma of the female breast: analysis of cosmesis and the role of electron beam supplementation. Int J Radiat Oncol Biol Phys 1983; 9:813-818.
diat
irradiated
breast.
AJR
1987;
148:39-43.
Schnitt SJ, Connolly JL, Recht A, et al. Breast relapse following primary radiation therapy for early breast cancer. II. Detection, pathologic features and prognostic significance. Int J Radiat Oncol Biol Phys 1985; 11:1277-1284. Paulus DP. Mammography of the treated breast (syllabus). Reston, Va: American College of Radiology, 1988; 49-57. Paulus
DP.
Conservative
treatment
of breast
cancer: mammography in patient selection and follow-up. AJR 1984; 143:483-487. Peters ME, Fagerholm MI, Scanlon KA, et al. Mammographic evaluation of the postsurgical and irradiated breast. RadioGraphics 1988; 8:813-899. Dershaw DD, Slak B, Reisinger S. Mammographic findings after breast cancer treatment with local excision and definitive irradiation. Radiology 1987; 164:455-461. Nisce LZ, Snyder RE, Chu FC. The role of mammography in evaluating radiation response of inoperable primary breast cancer. Radiology 1974; 110:85-88. Harris KM, Costa-Greco MA, Baratz AB, et al. The mammographic features of the postlumpectomy, postirradiation breast. RadioGraphics
1989;
9:253-268.
b.
a.
Volume
of the
RTT, and of patients
Fisher B, Redmond C, Poisson R, et al. Eightyear results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989; 320:822828. Sarrazin D, Le MG, Arriagada R, et a!. Tenyear results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer. Radiother Oncol 1989; 14:177-184. Veronesi U, Zucalli R, Luini A. Local control and survival in early breast cancer: the Milan trial. Int J Radiat Oncol Biol Phys 1986; 12:717-720.
conservation
months
Knistensen, for collation
References
8.
opacity
Marga-
Robertson,
in the preparation
manuscript and Sarah Robert Harrison, MSc, for the data base.
7.
Figure
thank
Manian
5.
Radial
scar.
(a)
Posttreatment
the area of surgery later shows decreased #{149} Number
mammogram
in the superior hemisphere. size of this opacity.
in
176
lateral
3
shows
ill-defined
(b) Mammogram
increased
obtained
7
Radiology
#{149} 735
R. Hassell, W. Kingston,
Gary
MD MD
#{149} Ivo #{149} Vivien
Early Breast of Recurrence Surgery and
A. Olivotto, E. Basco,
Cancer: after Radiation
To determine the clinical and mammographic features of recurrent breast cancer after tumorectomy and radiation therapy, the authors reviewed the clinical history and serial mammograms of 48 patients with suspected recurrence. Of patients with recurrent disease, seven had positive mammograms alone, nine had positive findings at physical examination alone, and eight had both positive mammograms and positive results of physical examination. Positive mammographic findings included the development of new fine calcifications (six patients), a new mass (five patients), mass and calcifications (one patient), increasing opacity (two patients), or skin thickening (one patient). Patients in whom the breast recurrence was detected mammographically alone were less likely to develop metastatic disease in subsequent follow-up than when results of physical examination were positive at the time of breast recurrence. Serial mammographic and clinical examinations are complementary for optimal detection of recurrence after conservative surgery and radiation therapy. Index Breast
terms: Breast, calcification, neoplasms, diagnosis, 00.32
plasms,
postoperative,
plasms,
therapy,
00.45
00.81
#{149}
Breast neo-
neo-
#{149}
Breast
#{149}
MD MD
#{149} Helmut
MD
Detection Conservative Therapy’
C
ONSERVATIVE surgery followed by radiation therapy has become an accepted treatment for women with stage I and II breast cancer. Three modern, prospective, randomized trials with long-term follow-up demonstrated no adverse effect on rates of overall survival or local control when the efficacy of conservative surgery and radiation therapy
was
compared
with
that
of total
mas-
tectomy (1-3). The combination of conservative surgery and radiation therapy offers the additional advantage of preserving the breast, usually with a highly satisfactory cosmetic result (4-6). Local failure of treatment can still be salvaged by further surgery, with 63%-69% of patients remaining free of further local on distant disease at 5 years after a recurrence of operable cancer of the breast (7,8). Early detection of these treatment failures may improve salvage rates. The role of mammography in the follow-up of patients undergoing conservative surgery and radiation therapy is not well defined. This report describes our experience with 48 patients who had suspected recurrence of breast cancer after conservative surgery and radiation therapy for stage I or II breast cancer.
00.1299
PATIENTS Radiology
A. Mueller,
1990;
AND
METHODS
176:731-735
The
British Columbia Cancer Agency is a regional cancer treatment center that serves a population of more than 3 million. Since 1979, conservative (BCCA)
surgery
From the Divisions of Diagnostic Imaging (P.R.H., HAM.) and Radiation Oncology (LAO., V.E.B.), British Columbia Cancer Agency, 600 W 10th Aye, Vancouver, BC V5Z 4E6, Canada; and the Department of Surgery, University of British Columbia, Vancouver (lAO., G.W.K., V.E.B.). From the 1989 RSNA scientific I
assembly.
Received
requested
November
May
7, 1990;
requests C
RSNA,
accepted
to P.R.H. 1990
October
12, 1989;
13; final May
revision
21. Address
revision
received reprint
Imaging
and
radiation
therapy
have
been
used increasingly for women with stage I and II (Union Internationale Contre be Cancer) breast cancer. Surgery consisted of excision of the primary tumor with a 1 -2-cm margin of grossly normal tissue and an axillary node dissection. Radiation therapy consisted of a tangent pair to the breast; a tumor dose of 44 Gy was delivered in 16 fractions over 31/2 weeks. A boost with cobalt or 7-1 1-MeV electrons with a given dose of 5 Gy in two fractions
was added to the primary site in approximately one-third of patients, generally when the margins were close on involved on a microscopic level. The regional nodes received a tumor dose of 37.5 Gy in 16 fractions from a direct internal mammary field and opposed supraclavicularaxillary fields. Nodal irradiation was used in all patients who had involved nodes in the early years but selectively in patients with a high risk of recurrence, such as those with more than four involved nodes on those demonstrating extranodal extension of disease in the later years. After treatment was complete, patients were followed up by means of physical examination at the BCCA or in conjunclion with the referring surgeon at 3-6month intervals. Mammograms of the treated breast were obtained every 6 months for 3 years and yearly thereafter. The contralateral breast was examined mammographicabby once a year. Mammograms obtained at BCCA were solely xeromammograms until December 1987 and screen-film mammograms thereafter. Xenomammograms were available for neview in 28 patients, and screen-film mammograrns were available in 16 patients. Patients included in this study were drawn from two sources. Our institution maintains a data base of 348 consecutive women treated between 1979 and 1985. Forty-three
patients
who
underwent
open biopsy of the treated breast for suspected recurrence were identified and included. Twenty-one patients had malignant disease at biopsy, 21 had benign changes, and one patient had initial benign biopsy results and later developed another mass that biopsy results confirmed as a recurrent malignancy. We identified an additional five consecutive patients (two with malignancy and three with benign biopsy results) from the private practice of two authors (I.A.O., V.E.B.) in 1986 and 1987. Therefore, the study population includes 48 women who underwent 49 biopsies for suspected recurrence of cancer in the treated breast aften conservative surgery and radiation therapy.
Abbreviation: Cancer
BCAA
=
British
Columbia
Agency.
731
For this study, the clinical, surgical, and pathologic records were reviewed. All available mammograms, including those obtained prior to the original diagnosis, after treatment, and immediately prior to the biopsy for suspected recurrence, were obtained and reviewed independently and subsequently by two radiobogists (P.R.H., H.A.M.). Mammograms were considered suspect for recurrent disease if there was evidence of (a) new fine calcifications, (b) a new mass that deveboped in comparison with the baseline mammogram obtained 6 months after treatment, (c) an increase in architectural distortion or opacity of the breast parenchyma, or (d) an increase in the skin thickening after the posttreatment changes had subsided. All patients with further cancer anywhere in the treated breast were considered to have recurrence. The median age of the 48 patients at the time of diagnosis was 53 years, with a range of 22-84 years. The initial pathologic diagnosis was ductal carcinoma in 40 patients, lobular carcinoma in five patients, colboid carcinoma in two patients, and medullary carcinoma in one patient.
were proved to have recurrent cancinoma. Twenty-two recurrent cancers were confirmed by means of open biopsy and two at autopsy. Results of histologic examination of the recurrent cancers were identical to results of such examination of the original primary tumor in 23 of 24 patients (96%). Recurrences were related to the primary site in 21 of 24 patients (88%). Two patients had involvement of the entire breast, and one patient developed a new mass in a quadrant
different from that of the original carcinoma. Table 1 demonstrates the original indication for biopsy as described in the clinical chart. The results of approximately 50% of biopsies performed because of suspicion after mammography (seven of 13 biopsies) or clinical examination (14 of 29 biopsies) were positive. Clinical suspicion was based on the presence of a mass on new thickening in all instances. The one patient in Table 1 in
RESULTS The median time from diagnosis to subsequent biopsy for suspected recurrence was 24 months (range, 4-59 months). Patients with benign biopsy results tended to undergo biopsies in the earlier period of follow-up. The median time from diagnosis to benign findings at biopsy was 15 months (range, 4-53 months). The median time from diagnosis to biopsy that proved malignancy was 28 months (range, 6-59 months). A total of 23 of 25 patients with benign findings at biopsy were alive when last examined 3-102 months after biopsy, compared with 17 of 24 patients with biopsy-proved malignancy who were last examined 1-49 months after diagnosis of recurrence. Twenty-four of the 48 patients
a.
b.
(a) Mammogram obtained 1 1 months after treatment shows architectural hon and radiation-induced skin thickening. (b) Mammogram obtained 25 months ment shows the development of malignant calcifications posterior to the previous resection site. Note reduction in skin thickening. Results of biopsy demonstrated infiltrating ductal carcinoma. Figure
732
#{149} Radiology
1.
distorafter treatsegmental in situ and
September
1990
whom biopsy was indicated for en” reasons underwent mastectomy for sive
not
cosmetic breast suspected
clinicably at that time, but at mastectomy the patient was found to have extensive disease recurrence. Twenty-two of the 24 patients found to have recurrent breast malig-
“oth-
reasons due to progresfibrosis. Recurrence was mammognaphicalby on
nancy underwent mammography within 4 months prior to the diagnosis of that recurrence. On review, the mammographic findings were positive in 15 patients (68%) and negative in seven patients (32%) (Table 2). Five of the six patients who developed calcification as the sole manifestation of recurrent disease had infiltrating and in situ carcinoma, and one patient had in situ ductab carcinoma alone (Fig 1). These patients are all alive, of 35 months
b. Figure 2. (a) Posttreatment region. (b) Mammogram in the inferior hemisphere. carcinoma.
craniocaudal view shows postoperative changes in the areobar obtained 25 months later shows a mass 1.2 cm in diameter (arrow) Pathologic findings indicated the presence of a second primary
with a median (range, 21-61
follow-up months)
after recurrence and without evidence of local or distant metastatic disease. Mammograms revealed a new mass in five of the 24 patients. The results of concurrent physical examination were positive in four patients. Two of these have since died of metastatic disease, one is alive with lung metastasis, and one is alive and well. The one patient with negative results of physical examination had a mass 1.2 cm in diameter in a different quadrant and of different histologic charactenistics than the original primary tumor; this mass likely represents a new primary tumor but was scored as a recurrence for this report (Fig 2). One patient had a new mass and calcifications with negative results of physical examination. She is alive and well. The results of physical examination were positive in both patients with increasing architectural distontion and breast opacity. One patient died of metastatic disease, and one is alive without evidence of further bocal or distant metastases. One patient showed increased skin thickening only. This developed after the skin thickening associated with surgery and radiation therapy had subsided. She subsequently developed distant metastases and died (Fig 3). Seven patients had negative mammograms. The diagnosis was made on the basis of clinically increasing nodulanity on mass at physical examination. Three of these patients are alive without metastasis, two are alive with active disease, and two have died of metastatic disease. Two patients without prior mammograph-
I Figure months
b.
Volume
176
#{149} Number
3
3. after
(a) Mammogram treatment
obtained shows
minimal
18 re-
sidual treatment-induced skin thickening. (b) Mammogram obtained 19 months later shows the development of marked skin thickening and increased parenchymal breast opacity.
Radiology
#{149} 733
ic evaluation underwent an open opsy, the results of which confirmed recurrence. Both died of metastatic disease. Twenty-five patients underwent
bi-
biopsies the findings of which were benign. The pathologic findings of these biopsies included radiation fibrosis, hematoma, cysts, fibroadenoma, foreign body reaction, and fat necrosis. Six of these biopsies were prompted by the original nadiobogist’s concern about the mass and opacity at the primary site; four patients had abnormal mammograms and a suspect physical examination, and 15 patients underwent biopsy for clinical indications only with no radiobogic suspicion of abnormality. In 22 of these 25 patients, mammograms were obtained within 4 months of the biopsy. On review of serial posttneatment mammograms (Table 3), only two of 22 patients were classified as suspect for recurrent malignancy according to the cnitenia in this report. One of these patients had a well-defined mass 1 .6 cm in diameter with a central coarse calcification. The mass increased slightby to 1 .8 in diameter 1 1 months later, and biopsy findings confirmed the presence of a fibroadenoma. The othen false-positive mammogram was an initial posttneatment image that showed increased opacity in the area where surgery was performed; this opacity was due to scarring at biopsy. In nine additional patients, a mass or opacity at the primary site was identified on the first posttreatment “baseline” study. In this review, these mammographic changes were therefore not considered suspect, although in some cases the posttreatment changes had been of sufficient concern to prompt a recommendation for biopsy by a radiologist from another institution (Figs 4, 5).
to be maximal at 6 months and to stabilize or resolve with time. Although the findings of recurrent breast cancer may be similar to those seen as a result of surgery and radiation treatment, the pattern of change with time should suggest the diagnosis. Compression magnification views may increase the ability to define changes at the primary site. The reappearance of skin thickening, or an increase in breast opacity alone after the skin thickening due to surgery and radiation treatment has decreased, should be considered highly suspect for recurrent breast cancer (13,15), even in the absence of other findings. The benign changes seen in the region of the surgery include increased opacity, stellate masses, or both. These can be difficult to differentiate from residuab or recurrent disease. However, these findings should either stabilize or decrease with time if they are due to postoperative scarring, hematoma, or seroma (11,16). Also, the margins of hematomas or seromas tend to be well defined and the masses more homogeneous than in recurrent cancer. Hematomas can persist unchanged for years (12). The use of ultrasound and aspiration is extremely helpful in these patients and may make a repeat biopsy unnecessary. Obtaining a posttreatment mammogram within the first 6 months after radiation therapy will provide a baseline study at a time when it is unlikely that
recurrence will already be developing. Subsequent mammograms can then be compared with this baseline as a reference to the amount of surgical and radiation change within the treated breast. Because the mammographic findings of recurrent disease are often subtle, mammograms of the highest quality are essential and serial observations are vital to detect early changes. The site of recurrence in this series and as reported previously (1,9,10) was usually in the same quadrant as the segmental resection. This area must be optimably imaged. Because of distortion to the breast, optimal imaging may be difficult and may require additional views. Magnification views can be helpful and are recommended selectively in patients in whom new mammographic findings have developed.
DISCUSSION Serial clinical and mammographic follow-up is essential in the detection of recurrent breast cancer. The frequency of negative mammograms (seven of 22 patients) and the substantial proportion of recurrences not detected at dinical examination (seven of 24 patients) in this series have been reported previously (9,10) and emphasize the importance of complementary clinical and mammographic follow-up. The mammographic findings after segmental resection and radiation treatment include increased skin thickening and increased parenchymal opacity of the breast. These have been well described (11-14). Treatment changes tend 734
#{149} Radiology
a.
b.
Figure 4. (a) Mammogram obtained 16 months after segmental defined bobulated mass 5.0 cm in diameter in the area of surgery, ma or seroma. (b) The mass is slightly smaller on this mammogram,
resection shows a sharply consistent with a hematoobtained 4 months later.
September
1990
All six patients in this series who had new fine calcifications as an isolated abnormality had recurrent disease. Unlike patients in previous reports (9,10), five of the six patients had infiltrating ductal as well as in situ carcinoma, and only one patient had carcinoma in situ alone. The development of new coarse calcifications was not unusual and was not considered suggestive of malignancy. Of the patients in whom the diagnosis of recurrent cancer was made on the basis of mammographic findings alone, all did well subsequent to mammography, with no evidence of distant metastasis or death in seven patients 25-53 months after treatment of the recurrence. Patients whose recurrence appeared clinically, with or without positive mammograms, did poorly; 12 of 17 died of disease or were alive with distant metastases, reflecting a more mabignant course of disease. The optimal timing and frequency of follow-up mammography has not been established. Recht et ab (7) analyzed the time course of treatment failure after
conservative surgery and radiation therapy and showed that the risk of ipsibateral breast cancer recurrence peaks at a rate of 2.5% per year between 2 and 6 years after treatment. The risk of recurrent breast cancer then diminishes, but patients remain at risk even 10 years after treatment (8,10); many of the “recurrences” beyond 10 years may represent the development of a new primary cancer (8). Our policy of obtaining mammograms of the treated breast at 6-month intervals and mammograms of the opposite breast at 12-month intervals was established as part of an ongoing study to determine the optimal frequency of mammograms because recurrence in the breast can be treated for cure. We still have too few recurrences to assess optimal frequency. At present we continue to recommend physical examination at least once every 6 months, mammography of the treated breast at least once every 6 months, and mammography of the contralateral breast once a year. U
Acknowledgment: ret Buchwitz
AIMBI,
The authors and
Sarah
for assistance
1.
2.
3.
4.
5.
6.
Rose
MA, Olivotto
9.
11.
12.
13.
14.
15.
16.
B, et al.
Conser-
Recht A, Silen W, Schnitt SJ, et al. Timecourse of local recurrence following conservative surgery and radiation therapy for early stage breast cancer. Int J Radiat Oncol Biol Phys Kurtz second
1988; 15:255-261. JM, Amalric R, Delouche C, et al. The ten years: long term risks of breast
in early
Oncol
Biol
Phys
breast
cancer.
1987;
Int J Ra-
13:1327-1332.
Stomper PC, Recht A, Berenberg AL, et al. Mammographic detection of recurrent cancer in the
10.
IA, Cady
vative surgery and radiation therapy for early breast cancer: long-term cosmetic results. Arch Surg 1989; 124:153-157. Clarke D, Martinez A, Cox RS. Analysis of cosmetic results and complications in patients with stage I and II breast cancer treated by biopsy and irradiation. Int J Radiat Oncol Biol Phys 1983; 9:1807-1813. Ray GR, Fish VJ. Biopsy and definitive radiation therapy in stage I and II adenocarcinoma of the female breast: analysis of cosmesis and the role of electron beam supplementation. Int J Radiat Oncol Biol Phys 1983; 9:813-818.
diat
irradiated
breast.
AJR
1987;
148:39-43.
Schnitt SJ, Connolly JL, Recht A, et al. Breast relapse following primary radiation therapy for early breast cancer. II. Detection, pathologic features and prognostic significance. Int J Radiat Oncol Biol Phys 1985; 11:1277-1284. Paulus DP. Mammography of the treated breast (syllabus). Reston, Va: American College of Radiology, 1988; 49-57. Paulus
DP.
Conservative
treatment
of breast
cancer: mammography in patient selection and follow-up. AJR 1984; 143:483-487. Peters ME, Fagerholm MI, Scanlon KA, et al. Mammographic evaluation of the postsurgical and irradiated breast. RadioGraphics 1988; 8:813-899. Dershaw DD, Slak B, Reisinger S. Mammographic findings after breast cancer treatment with local excision and definitive irradiation. Radiology 1987; 164:455-461. Nisce LZ, Snyder RE, Chu FC. The role of mammography in evaluating radiation response of inoperable primary breast cancer. Radiology 1974; 110:85-88. Harris KM, Costa-Greco MA, Baratz AB, et al. The mammographic features of the postlumpectomy, postirradiation breast. RadioGraphics
1989;
9:253-268.
b.
a.
Volume
of the
RTT, and of patients
Fisher B, Redmond C, Poisson R, et al. Eightyear results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989; 320:822828. Sarrazin D, Le MG, Arriagada R, et a!. Tenyear results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer. Radiother Oncol 1989; 14:177-184. Veronesi U, Zucalli R, Luini A. Local control and survival in early breast cancer: the Milan trial. Int J Radiat Oncol Biol Phys 1986; 12:717-720.
conservation
months
Knistensen, for collation
References
8.
opacity
Marga-
Robertson,
in the preparation
manuscript and Sarah Robert Harrison, MSc, for the data base.
7.
Figure
thank
Manian
5.
Radial
scar.
(a)
Posttreatment
the area of surgery later shows decreased #{149} Number
mammogram
in the superior hemisphere. size of this opacity.
in
176
lateral
3
shows
ill-defined
(b) Mammogram
increased
obtained
7
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