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Inflammatory carcinoma of the breast
Inflammatory Carcinoma of the Breast A Therapeutic Approach Followed by Improved Survival
Erich W. Pollak, MD, FACS, Kansas City, Missouri Lindsay C. Getzen, MD, FACS, Davis, California
Inflammatory carcinoma of the breast, a relatively infrequent clinicopathologic entity, is characterized by a high grade of malignant adenocarcinoma of the breast, with extensive involvement and blockade of dermal and subdermal lymphatics and erythema, hyperemia, and edema of the overlying skin. Controversy persists regarding the best available treatment for this disease because of its known poor prognosis with any kind of treatment. The following results were obtained with combination therapy in a small series of patients in whom improved length of survival was achieved. Material and Methods
A clinical diagnosis of inflammatory carcinoma of the breast was made in thirteen patients at the United States Naval Hospitals of Bethesda, Maryland and San Diego, California, and at the Sacramento Medical Center, Sacramento, California, during the ten year period between 1964 to 1973. Nine of these patients met the histologic criteria for diagnosis (involvement and blockade of dermal and subdermal lymphatics by cancer cells). Only these nine patients will be considered further in this study. All patients were women of ages ranging from forty-three to sixty-six years (mean, 54 f 8 years). All presented with local pain and erythema of the skin and an underlying breast mass. Typical “peau d’orange” was present in four, and axillary metastasis was present in eight. In two patients (group A), once the diagnosis was established by biopsy, the following treatment was administered: (1) radiation therapy to the breast region and axilla (1 received a total radiation dose of 7,500 rad and 1 received a dose of 5,000 rad) and (2) oophorectomy and adrenalectomy. (Table I.) The remaining seven patients (group B) were treated as From the Department of Surgery, University of Missouri at Kansas City, Kansas City, Missouri, and University of California at Davis, Davis, California. The opinions or assertions contained herein are those of the authors and are not to be construed as official or as reflecting the view of the U.S. Department of the Navy. Reprint requests should be addressed to Erich W. Pollak. MD, 8940 Mall Avenue, Overland Park, Kansas 66207. Presented at the Thirtieth Annual Meeting of the Southwestern Surgical Congress, Palm Springs, California, April 17-20. 1978.
722
follows: (1) preoperative radiation therapy 2,000 to 3,500 rad (6 patients); (2) radical mastectomy (all 7 patients); (3) oophorectomy (5 patients); (4) postoperative radiation therapy to the chest wall and axilla up to a total dose of 5,000 rad (all 7 patients); and (5) thiotepa administration (all 7 patients). (Table I.) Posttreatment follow-up data until death or for a minimum of five and a half years in survivors were documented for all patients. Results
As shown in Table I, the two patients treated with radiation therapy, oophorectomy, and adrenalectomy survived five and eight months and succumbed from metastatic disease. Of the seven patients treated with radiation therapy, radical mastectomy, and chemotherapy, one patient who had been treated for adenocarcinoma of the right breast eight years before consulting for inflammatory adenocarcinoma of the left breast, survived for five years after therapy for inflammatory carcinoma and died due to metastatic disease from an unrelated adenocarcinoma of the gallbladder. Four patients died 13, 16, 37, and 42 months after treatment of metastatic disease. The remaining two patients were alive and clinically free of metastatic disease five and a half and seven years after treatment. (Table I.) Comments
Inflammatory carcinoma accounts only for 2.4 per cent of all breast cancers [I]. Clinical debut occurred most frequently during the fifth decade of life, at a time when true inflammatory processes of the breast were less frequent [2]. However, a review of cases showed that a clinical diagnosis of mastitis was frequently made and treatment trials with antibiotics were instated in most patients with inflammatory carcinoma of the breast, thus delaying further the diagnosis of cancer. Recent statistics show that the incidence of such diagnostic error has been increasing during the last few years [I]; thus, the necessity for
The American Journal of Surgery
Inflammatory
early histologic diagnosis should be emphasized, even if historically results of therapy have been discouraging in what seemed to be instances of “early” diagnosis and treatment of inflammatory carcinoma of the breast. W’hether inflammatory carcinoma is a distinct disease entity is highly questionable. Cytologic and histologic investigations failed to produce support for s,uch belief, and objective findings suggested instead that inflammatory carcinoma is only an advanced stage of breast cancer with lymphatic blockade by intralymphatic tumor extension and invasion of skin and subdermal layers. Average survival of patients varied from twelve to twenty-eight months in diverse series [3] regardless of therapy. Although fe?w isolated instances of long-term survivors have been reported, fewer than 50 per cent of patients were alive one year after diagnosis. Only 17 per cent survived three years, and 3 to 5.5 per cent survived five years or more [I,4]. A review of therapeutic procedures used in the past showed the inability of radiotherapy, surgery, or chemotherapy alone to cure most instances of inflammatory breast carcinoma [5]. An unacceptable rate of postoperative local recurrence and death from metastatic disease followed exclusive use of radical mastectomy [6], caused probably by dissemination of cancer during operative transection of lymphatics colonized by tumor or decreased immunologic defenses after operation. Radiation therapy achieved better local control of cancer than did operation [4], and on these grounds, rad:.cal mastectomy was abandoned in many centers and radiotherapy used instead. However, it soon became apparent that local control of disease by radiation therapy was only transient in most cases, and no improved length of survival followed nonoperative treatment. In a series of 411 patients treated with diverse methods, the five year survival rate was 3.1 per cent. This series included 166 patients treated solely with irradiation, their five year survival rate being only 1.8 per cent [3]. In another more recent series, three patients receiving only radiotherapy survived three, twelve, and eighteen months; another five patients treated with irradiation combined with hormonal therapy and/or chemotherapy survived an average of twenty-one months, whereas ten patients whose treatment included radical mastectomy survived an average of thirty-two months [2]. Poor survival after a combination of irradiation and endocrine ablation (oophorectomy and adrenalectomy) has also been reported and was corroborated by results in our series. (Table I.) Although good objective responses (that is, reduction in size of primary and
Volume 136, December 1976
TABLE I
Breast Carcinoma
Age and Survival of Patients with Inflammatory Carcinoma of the Breast Survival (mo)
Patient
Age (yr)
Group A’ 1 2
58 55
a 5
64 66 49 48 47 43 53
60 13 16 >84 42 >66 37
Group Bt
3 4 5 6 7 8 9
Treated with radiation therapy, oophorectomy, and adrenalectomy. + Treated with radical mastectomy, radiation therapy, and chemotherapy. l
metastatic lesions) were observed, survival time of these patients was shorter than that of patients treated with radical mastectomy [2]. Objective analysis of results obtained with all presently available therapeutic methods suggests that although results of radical mastectomy were meager in the treatment of inflammatory breast carcinoma, results were even worse in those instances in which radical mastectomy was not performed. Our results (Table I) and those of others showed no rational basis on which to contraindicate radical mastectomy for inflammatory breast carcinoma, as postulated by some [5,6]. Moreover, data presented herein showed that combined therapy in seven patients, including radical mastectomy, pre- and postoperative radiation therapy, and chemotherapy, led to significantly better results (mean survival, 45.5 f 26.2 months) than did the combination of radiation therapy with oophorectomy and adrenalectomy in two patients (mean survival, 6.6 f 2.1 months; p < 0.05). We consider inflammatory carcinoma to be an advanced stage of breast cancer, with massive local invasion and generalized circulation of cancer cells. Consequently, preoperative radiation therapy was used to control tumor mass and local spread. Local removal of tumor was then completed by radical mastectomy, and postoperative radiation was used to control tumor spread from possible residual cancer located in lymphatic channels transected during operation. Chemotherapy was added to control circulating tumor cells and remote microscopic deposits of tumor inaccessible to operation and radiation. To this combination therapy we would now add oophorectomy and adrenalectomy in patients with estrogen-dependent tumors for treatment of inaccessible metastatic disease.
723
Pollack and Getzen
Critical review of results of combined therapy as outlined herein showed that this treatment could improve the meager results of previously used therapy for inflammatory breast carcinoma. However, further improvement is needed, and it is more likely to come from new forms of chemotherapy rather than from further sophistication of radiation therapy, resective operations, and hormonal manipulation. Encouraging initial results were recently reported in a two year study with cyclic long-term combination chemotherapy using Adriamycin@, cyclophosphamide, .$fluorouracil, vincristine, and methotrexate and immunotherapy consisting of BCG vaccine [7]. It seems to us that the next logical step would be to explore sequential therapeutic variants comprising initial treatment of inflammatory breast carcinoma with combination therapy as outlined by us, followed by some form of cyclic long-term chemotherapyimmunotherapy. Summary
Disappointing results of radical mastectomy for treatment of inflammatory breast carcinoma led to its abandonment and the use of alternative therapeutic methods without improvement of survival rates. Results of radical mastectomy combined with other therapeutic modalities have not been fully evaluated so far. In a series of nine patients with proven inflammatory breast carcinoma and no distant metastases, two underwent radiotherapy, oophorectomy, and adrenalectomy (group A) and seven underwent preoperative irradiation, radical mastectomy, postoperative irradiation, and chemotherapy (group B). There were no local recurrences in either group. Group A patients survived five and eight months (mean, 6.6 f 2.1) and patients of group B survived 45.5 f 26.2 months (p < 0.05). Results show no rational basis for withholding radical mastectomy, but suggest that improved survival may be obtained when radical mastectomy is an integral part of a rational sequential therapeutic schedule. References 1. Droulias CA, Sewell CW, McSweeney MB, et al: Inflammatory carcinoma of the breast. A correlation of clinical radiologic and pathologic findings. Ann Surg 184: 217, 1976. 2. Stocks LH, Patterson FM: Inflammatory carcinoma of the breast. Surg Gynecol Obstet 143: 885, 1976. 3. Yonemoto RH, Keating JL, Byron RL. et al: Inflammatory carcinoma of the breast treated by bilateral adrenalectomy. Surgery 68: 461, 1970. 4. Barker JL. Nelson AJ, Montague ED: Inflammatory carcinoma of the breast. Radiology 121: 173, 1976. 5. Robbins GF, Shah J, Rosen P, et al: Inflammatory carcinoma of the breast. Surg C/in North Am 54(4): 801, 1974.
724
6. Wang CC: Management of inflammatory carcinoma of the breast. JAMA 201: 123,1967. 7. Blumenschein GR, Montague ED, Eckles NE, et al: Sequential combined modality therapy for inflammatory breast cancer. Breast 2: 16. 1976.
Discussion Charles Kruse (Santa Monica, CA): It may be that the authors’ improvement of survival correlated with so-called “localized” inflammatory carcinoma of the breast, as the liver and bone scans were negative in their nine patients reported in detail with their histologic criteria. No supraclavicular nodes were observed, thus allowing a regimen of pre- and postoperative radiation, radical mastectomy, and single agent chemotherapy as their method of treatment, which has given better results than experience of others has shown to date. The use of radical mastectomy has been considered contraindicated by most authors in view of the generalized nature of the disease when the patient is first seen. None of the patients in this series had the estrogen receptor test done, as they were all treated prior to 1973. A recent series of fifty-four cases of inflammatory carcinoma was reported in 1977 from the Kaiser Permanente Center in Los Angeles using radiation therapy and multiple agent chemotherapy, a number of their patients having hormonal ablative procedures. Estrogen receptor protein tests were not done, but eleven of the fifty-four patients survived longer than two years; however, seven of these started with adrenalectomy and oophorectomy, attesting to the value of the systemic form of hormone ablation rather than localized treatment. Their longest survivor lived seven years, and her only treatment was hormone ablation. They do not believe that dermal invasion is necessary for the clinical diagnosis; in fact, some of their patients who had dermal invasion lived slightly longer than those who did not. They interpret this as indicating that systemic treatment is the most important factor in determining survival. Finally, as pointed out by Alfred Frachea of Memorial Hospital in New York, patients with a positive estrogen binding test and a positive progesterone binding test will show more than 80 per cent response to appropriate ablative endocrine surgery. In patients with negative estrogen and progesterone binding, there is less than 5 per cent response to hormonal manipulation, whether additive or with deprivation. Nathaniel M. Matolo (Davis, CA): It is very obvious in reviewing their small series of patients, that combined irradiation therapy, radical mastectomy, and chemotherapy led to a better survival than did irradiation and endocrine ablation. Their results are very encouraging in the management of this lethal and aggressive form of breast cancer. However, their series is too small; a larger, probably more controlled, series is needed to confirm these findings. It should be emphasized that inflammatory carcinoma of the breast is very malignant; the tumor cells are usually undifferentiated and the subdermal lymphatics are widely
The American Journal of Surgery
Inflammatory
irwolved with carcinoma. As a result, there is an acute onset of redness, pain, and swelling of the breast due to lymphatic blot:kade and lymphangitis. The breast is hot and grossly appears to be involved with cellulitis. Not only are skin Iymphatics full of tumor cells but so are the surface veins ant axillary lymph nodes on many occasions. In general, the prognosis is very grave, and treatment is usually inadequate to control the disease. Additionally, were all patients who underwent oophorect .rmy and adrenalectomy premenopausal? Did you have any’ wound healing problems in those patients who received preoperative radiation therapy?
Kent C. Westbrook (Little Rock, AR): I commend the authors for taking an aggressive attitude towards essentially incurable disease. However, we have to keep one thing carefully in mind, that this is essentially a systemic disease, and local therapy probably is not going to alter the longterm survival, and the systemic treatment is that based on estrogen receptors and multidrug therapy. 1 think the authors must be seeing a different type of inflammatory carcinoma than I am seeing. (Slide) This is a thirty-two year old bank teller who came in recently for advanced cancer with -inflammatory changes extending around to the midline and the back, across metastases to the other side. (Slide) This is a woman with inflammatory breast cancer extending all over her upper trunk. (Slide) This is a patient with a more typical lesion, but she has massive supraclavicular metastases, massive axillary metastases, and swelling of the arm. I am sure that the authors probably would not recommend radical mastectomy in this group of patients. I think their results are due primarily to selection of patients for this locally aggressive form of therapy. I have one question. What patients with red swollen breasts and breast cancer do you recommend to undergo radical mastectomy?
Claude H. Organ (Omaha, NB): These are very unusual results, and I agree with Dr. Westbrook that the type of in:?lammatory carcinoma we are seeing is a little different. There are differences between inflammatory carcinoma of the breast and adenocarcinoma of the breast with inflammation in the degree of breast involvement, biologic
Volume 136, December 1976
activity, prognosis, and indeed, tion is in order about this.
Breast Carcinoma
treatment.
A word of cau-
Erich W. Pollak (closing): As stated by Dr. Kruse, tumors not meeting the histologic criteria of inflammatory carcinoma have been labeled as such by some authors. As emphasized by Dr. Organ, histologic verification of diagnosis is necessary before therapeutic conclusions can be advanced. Our series did not include terminally ill patients as those shown by Dr. Westbrook, and we did not intend to refer to such patients. Review of the literature showed that exclusion of radical mastectomy from the treatment plan did not increase but rather decreased length of survival in inflammatory breast carcinoma patients” Moreover, it showed that such exclusion was based upon an erroneous concept about the role of operation in this disease. Earlier, operation was intended for complete tumor eradication; however,it has been shown that this is impossible because of the existence of circulating tumor cells since early stages of the disease. The modern concept is completely different. We remove as much as possible of the tumor, thus enabling the immunologic mechanisms of the body to eliminate the residual cancer, to arrest the tumor growth, or at least to reach a biologic equilibrium between the body and the tumor. When radical mastectomy is analyzed within this context, the radical mastectomy is intended to remove tumor mass in patients with inflammatory breast cancer. It is part of the treatment, not the exclusive treatment. The real problem for the practicing physician in 1978 is to decide what to do with all this new knowledge. There seems to be enough evidence to support the use of endocrine ablation in patients who have breast tumors with estrogen receptors. However, some ER-negative patients also respond favorably to endocrine ablation. Consequently it is our personal opinion that we probably cannot withhold the benefits of endocrine ablation from these patients just because there will be a few responders, because there are no really good alternatives to treatment of this very lethal disease. We did have some problem with wound healing but no local recurrence of cancer. The doses of preoperative and postoperative radiation will depend on the t,ype of equipment, radiation technic, and individual characteristics of the patient and would be better discussed by a radiotherapist than by a surgeon.
725
Erich W. Pollak, MD, FACS, Kansas City, Missouri Lindsay C. Getzen, MD, FACS, Davis, California
Inflammatory carcinoma of the breast, a relatively infrequent clinicopathologic entity, is characterized by a high grade of malignant adenocarcinoma of the breast, with extensive involvement and blockade of dermal and subdermal lymphatics and erythema, hyperemia, and edema of the overlying skin. Controversy persists regarding the best available treatment for this disease because of its known poor prognosis with any kind of treatment. The following results were obtained with combination therapy in a small series of patients in whom improved length of survival was achieved. Material and Methods
A clinical diagnosis of inflammatory carcinoma of the breast was made in thirteen patients at the United States Naval Hospitals of Bethesda, Maryland and San Diego, California, and at the Sacramento Medical Center, Sacramento, California, during the ten year period between 1964 to 1973. Nine of these patients met the histologic criteria for diagnosis (involvement and blockade of dermal and subdermal lymphatics by cancer cells). Only these nine patients will be considered further in this study. All patients were women of ages ranging from forty-three to sixty-six years (mean, 54 f 8 years). All presented with local pain and erythema of the skin and an underlying breast mass. Typical “peau d’orange” was present in four, and axillary metastasis was present in eight. In two patients (group A), once the diagnosis was established by biopsy, the following treatment was administered: (1) radiation therapy to the breast region and axilla (1 received a total radiation dose of 7,500 rad and 1 received a dose of 5,000 rad) and (2) oophorectomy and adrenalectomy. (Table I.) The remaining seven patients (group B) were treated as From the Department of Surgery, University of Missouri at Kansas City, Kansas City, Missouri, and University of California at Davis, Davis, California. The opinions or assertions contained herein are those of the authors and are not to be construed as official or as reflecting the view of the U.S. Department of the Navy. Reprint requests should be addressed to Erich W. Pollak. MD, 8940 Mall Avenue, Overland Park, Kansas 66207. Presented at the Thirtieth Annual Meeting of the Southwestern Surgical Congress, Palm Springs, California, April 17-20. 1978.
722
follows: (1) preoperative radiation therapy 2,000 to 3,500 rad (6 patients); (2) radical mastectomy (all 7 patients); (3) oophorectomy (5 patients); (4) postoperative radiation therapy to the chest wall and axilla up to a total dose of 5,000 rad (all 7 patients); and (5) thiotepa administration (all 7 patients). (Table I.) Posttreatment follow-up data until death or for a minimum of five and a half years in survivors were documented for all patients. Results
As shown in Table I, the two patients treated with radiation therapy, oophorectomy, and adrenalectomy survived five and eight months and succumbed from metastatic disease. Of the seven patients treated with radiation therapy, radical mastectomy, and chemotherapy, one patient who had been treated for adenocarcinoma of the right breast eight years before consulting for inflammatory adenocarcinoma of the left breast, survived for five years after therapy for inflammatory carcinoma and died due to metastatic disease from an unrelated adenocarcinoma of the gallbladder. Four patients died 13, 16, 37, and 42 months after treatment of metastatic disease. The remaining two patients were alive and clinically free of metastatic disease five and a half and seven years after treatment. (Table I.) Comments
Inflammatory carcinoma accounts only for 2.4 per cent of all breast cancers [I]. Clinical debut occurred most frequently during the fifth decade of life, at a time when true inflammatory processes of the breast were less frequent [2]. However, a review of cases showed that a clinical diagnosis of mastitis was frequently made and treatment trials with antibiotics were instated in most patients with inflammatory carcinoma of the breast, thus delaying further the diagnosis of cancer. Recent statistics show that the incidence of such diagnostic error has been increasing during the last few years [I]; thus, the necessity for
The American Journal of Surgery
Inflammatory
early histologic diagnosis should be emphasized, even if historically results of therapy have been discouraging in what seemed to be instances of “early” diagnosis and treatment of inflammatory carcinoma of the breast. W’hether inflammatory carcinoma is a distinct disease entity is highly questionable. Cytologic and histologic investigations failed to produce support for s,uch belief, and objective findings suggested instead that inflammatory carcinoma is only an advanced stage of breast cancer with lymphatic blockade by intralymphatic tumor extension and invasion of skin and subdermal layers. Average survival of patients varied from twelve to twenty-eight months in diverse series [3] regardless of therapy. Although fe?w isolated instances of long-term survivors have been reported, fewer than 50 per cent of patients were alive one year after diagnosis. Only 17 per cent survived three years, and 3 to 5.5 per cent survived five years or more [I,4]. A review of therapeutic procedures used in the past showed the inability of radiotherapy, surgery, or chemotherapy alone to cure most instances of inflammatory breast carcinoma [5]. An unacceptable rate of postoperative local recurrence and death from metastatic disease followed exclusive use of radical mastectomy [6], caused probably by dissemination of cancer during operative transection of lymphatics colonized by tumor or decreased immunologic defenses after operation. Radiation therapy achieved better local control of cancer than did operation [4], and on these grounds, rad:.cal mastectomy was abandoned in many centers and radiotherapy used instead. However, it soon became apparent that local control of disease by radiation therapy was only transient in most cases, and no improved length of survival followed nonoperative treatment. In a series of 411 patients treated with diverse methods, the five year survival rate was 3.1 per cent. This series included 166 patients treated solely with irradiation, their five year survival rate being only 1.8 per cent [3]. In another more recent series, three patients receiving only radiotherapy survived three, twelve, and eighteen months; another five patients treated with irradiation combined with hormonal therapy and/or chemotherapy survived an average of twenty-one months, whereas ten patients whose treatment included radical mastectomy survived an average of thirty-two months [2]. Poor survival after a combination of irradiation and endocrine ablation (oophorectomy and adrenalectomy) has also been reported and was corroborated by results in our series. (Table I.) Although good objective responses (that is, reduction in size of primary and
Volume 136, December 1976
TABLE I
Breast Carcinoma
Age and Survival of Patients with Inflammatory Carcinoma of the Breast Survival (mo)
Patient
Age (yr)
Group A’ 1 2
58 55
a 5
64 66 49 48 47 43 53
60 13 16 >84 42 >66 37
Group Bt
3 4 5 6 7 8 9
Treated with radiation therapy, oophorectomy, and adrenalectomy. + Treated with radical mastectomy, radiation therapy, and chemotherapy. l
metastatic lesions) were observed, survival time of these patients was shorter than that of patients treated with radical mastectomy [2]. Objective analysis of results obtained with all presently available therapeutic methods suggests that although results of radical mastectomy were meager in the treatment of inflammatory breast carcinoma, results were even worse in those instances in which radical mastectomy was not performed. Our results (Table I) and those of others showed no rational basis on which to contraindicate radical mastectomy for inflammatory breast carcinoma, as postulated by some [5,6]. Moreover, data presented herein showed that combined therapy in seven patients, including radical mastectomy, pre- and postoperative radiation therapy, and chemotherapy, led to significantly better results (mean survival, 45.5 f 26.2 months) than did the combination of radiation therapy with oophorectomy and adrenalectomy in two patients (mean survival, 6.6 f 2.1 months; p < 0.05). We consider inflammatory carcinoma to be an advanced stage of breast cancer, with massive local invasion and generalized circulation of cancer cells. Consequently, preoperative radiation therapy was used to control tumor mass and local spread. Local removal of tumor was then completed by radical mastectomy, and postoperative radiation was used to control tumor spread from possible residual cancer located in lymphatic channels transected during operation. Chemotherapy was added to control circulating tumor cells and remote microscopic deposits of tumor inaccessible to operation and radiation. To this combination therapy we would now add oophorectomy and adrenalectomy in patients with estrogen-dependent tumors for treatment of inaccessible metastatic disease.
723
Pollack and Getzen
Critical review of results of combined therapy as outlined herein showed that this treatment could improve the meager results of previously used therapy for inflammatory breast carcinoma. However, further improvement is needed, and it is more likely to come from new forms of chemotherapy rather than from further sophistication of radiation therapy, resective operations, and hormonal manipulation. Encouraging initial results were recently reported in a two year study with cyclic long-term combination chemotherapy using Adriamycin@, cyclophosphamide, .$fluorouracil, vincristine, and methotrexate and immunotherapy consisting of BCG vaccine [7]. It seems to us that the next logical step would be to explore sequential therapeutic variants comprising initial treatment of inflammatory breast carcinoma with combination therapy as outlined by us, followed by some form of cyclic long-term chemotherapyimmunotherapy. Summary
Disappointing results of radical mastectomy for treatment of inflammatory breast carcinoma led to its abandonment and the use of alternative therapeutic methods without improvement of survival rates. Results of radical mastectomy combined with other therapeutic modalities have not been fully evaluated so far. In a series of nine patients with proven inflammatory breast carcinoma and no distant metastases, two underwent radiotherapy, oophorectomy, and adrenalectomy (group A) and seven underwent preoperative irradiation, radical mastectomy, postoperative irradiation, and chemotherapy (group B). There were no local recurrences in either group. Group A patients survived five and eight months (mean, 6.6 f 2.1) and patients of group B survived 45.5 f 26.2 months (p < 0.05). Results show no rational basis for withholding radical mastectomy, but suggest that improved survival may be obtained when radical mastectomy is an integral part of a rational sequential therapeutic schedule. References 1. Droulias CA, Sewell CW, McSweeney MB, et al: Inflammatory carcinoma of the breast. A correlation of clinical radiologic and pathologic findings. Ann Surg 184: 217, 1976. 2. Stocks LH, Patterson FM: Inflammatory carcinoma of the breast. Surg Gynecol Obstet 143: 885, 1976. 3. Yonemoto RH, Keating JL, Byron RL. et al: Inflammatory carcinoma of the breast treated by bilateral adrenalectomy. Surgery 68: 461, 1970. 4. Barker JL. Nelson AJ, Montague ED: Inflammatory carcinoma of the breast. Radiology 121: 173, 1976. 5. Robbins GF, Shah J, Rosen P, et al: Inflammatory carcinoma of the breast. Surg C/in North Am 54(4): 801, 1974.
724
6. Wang CC: Management of inflammatory carcinoma of the breast. JAMA 201: 123,1967. 7. Blumenschein GR, Montague ED, Eckles NE, et al: Sequential combined modality therapy for inflammatory breast cancer. Breast 2: 16. 1976.
Discussion Charles Kruse (Santa Monica, CA): It may be that the authors’ improvement of survival correlated with so-called “localized” inflammatory carcinoma of the breast, as the liver and bone scans were negative in their nine patients reported in detail with their histologic criteria. No supraclavicular nodes were observed, thus allowing a regimen of pre- and postoperative radiation, radical mastectomy, and single agent chemotherapy as their method of treatment, which has given better results than experience of others has shown to date. The use of radical mastectomy has been considered contraindicated by most authors in view of the generalized nature of the disease when the patient is first seen. None of the patients in this series had the estrogen receptor test done, as they were all treated prior to 1973. A recent series of fifty-four cases of inflammatory carcinoma was reported in 1977 from the Kaiser Permanente Center in Los Angeles using radiation therapy and multiple agent chemotherapy, a number of their patients having hormonal ablative procedures. Estrogen receptor protein tests were not done, but eleven of the fifty-four patients survived longer than two years; however, seven of these started with adrenalectomy and oophorectomy, attesting to the value of the systemic form of hormone ablation rather than localized treatment. Their longest survivor lived seven years, and her only treatment was hormone ablation. They do not believe that dermal invasion is necessary for the clinical diagnosis; in fact, some of their patients who had dermal invasion lived slightly longer than those who did not. They interpret this as indicating that systemic treatment is the most important factor in determining survival. Finally, as pointed out by Alfred Frachea of Memorial Hospital in New York, patients with a positive estrogen binding test and a positive progesterone binding test will show more than 80 per cent response to appropriate ablative endocrine surgery. In patients with negative estrogen and progesterone binding, there is less than 5 per cent response to hormonal manipulation, whether additive or with deprivation. Nathaniel M. Matolo (Davis, CA): It is very obvious in reviewing their small series of patients, that combined irradiation therapy, radical mastectomy, and chemotherapy led to a better survival than did irradiation and endocrine ablation. Their results are very encouraging in the management of this lethal and aggressive form of breast cancer. However, their series is too small; a larger, probably more controlled, series is needed to confirm these findings. It should be emphasized that inflammatory carcinoma of the breast is very malignant; the tumor cells are usually undifferentiated and the subdermal lymphatics are widely
The American Journal of Surgery
Inflammatory
irwolved with carcinoma. As a result, there is an acute onset of redness, pain, and swelling of the breast due to lymphatic blot:kade and lymphangitis. The breast is hot and grossly appears to be involved with cellulitis. Not only are skin Iymphatics full of tumor cells but so are the surface veins ant axillary lymph nodes on many occasions. In general, the prognosis is very grave, and treatment is usually inadequate to control the disease. Additionally, were all patients who underwent oophorect .rmy and adrenalectomy premenopausal? Did you have any’ wound healing problems in those patients who received preoperative radiation therapy?
Kent C. Westbrook (Little Rock, AR): I commend the authors for taking an aggressive attitude towards essentially incurable disease. However, we have to keep one thing carefully in mind, that this is essentially a systemic disease, and local therapy probably is not going to alter the longterm survival, and the systemic treatment is that based on estrogen receptors and multidrug therapy. 1 think the authors must be seeing a different type of inflammatory carcinoma than I am seeing. (Slide) This is a thirty-two year old bank teller who came in recently for advanced cancer with -inflammatory changes extending around to the midline and the back, across metastases to the other side. (Slide) This is a woman with inflammatory breast cancer extending all over her upper trunk. (Slide) This is a patient with a more typical lesion, but she has massive supraclavicular metastases, massive axillary metastases, and swelling of the arm. I am sure that the authors probably would not recommend radical mastectomy in this group of patients. I think their results are due primarily to selection of patients for this locally aggressive form of therapy. I have one question. What patients with red swollen breasts and breast cancer do you recommend to undergo radical mastectomy?
Claude H. Organ (Omaha, NB): These are very unusual results, and I agree with Dr. Westbrook that the type of in:?lammatory carcinoma we are seeing is a little different. There are differences between inflammatory carcinoma of the breast and adenocarcinoma of the breast with inflammation in the degree of breast involvement, biologic
Volume 136, December 1976
activity, prognosis, and indeed, tion is in order about this.
Breast Carcinoma
treatment.
A word of cau-
Erich W. Pollak (closing): As stated by Dr. Kruse, tumors not meeting the histologic criteria of inflammatory carcinoma have been labeled as such by some authors. As emphasized by Dr. Organ, histologic verification of diagnosis is necessary before therapeutic conclusions can be advanced. Our series did not include terminally ill patients as those shown by Dr. Westbrook, and we did not intend to refer to such patients. Review of the literature showed that exclusion of radical mastectomy from the treatment plan did not increase but rather decreased length of survival in inflammatory breast carcinoma patients” Moreover, it showed that such exclusion was based upon an erroneous concept about the role of operation in this disease. Earlier, operation was intended for complete tumor eradication; however,it has been shown that this is impossible because of the existence of circulating tumor cells since early stages of the disease. The modern concept is completely different. We remove as much as possible of the tumor, thus enabling the immunologic mechanisms of the body to eliminate the residual cancer, to arrest the tumor growth, or at least to reach a biologic equilibrium between the body and the tumor. When radical mastectomy is analyzed within this context, the radical mastectomy is intended to remove tumor mass in patients with inflammatory breast cancer. It is part of the treatment, not the exclusive treatment. The real problem for the practicing physician in 1978 is to decide what to do with all this new knowledge. There seems to be enough evidence to support the use of endocrine ablation in patients who have breast tumors with estrogen receptors. However, some ER-negative patients also respond favorably to endocrine ablation. Consequently it is our personal opinion that we probably cannot withhold the benefits of endocrine ablation from these patients just because there will be a few responders, because there are no really good alternatives to treatment of this very lethal disease. We did have some problem with wound healing but no local recurrence of cancer. The doses of preoperative and postoperative radiation will depend on the t,ype of equipment, radiation technic, and individual characteristics of the patient and would be better discussed by a radiotherapist than by a surgeon.
725