Site search
 
        

    BE A PARTNER . . . NOT A PATIENT

    The primary mission of the Texas Cancer Center is to show you the great body of medical evidence which supports conservative (limited) surgery for patients with cancer. Patients and doctors alike have a natural desire to eliminate every last cancer cell - "Get It ALL." Medical research tells us that the entire tumor should be removed. But, the surgeon does not need to perform radical surgery to eradicate nearby microscopic cells which might be cancerous. This treatment strategy has been proven to be successful for breast cancer, melanoma, the soft tissue sarcomas, and other cancers.

    For patients with breast cancer, removal of the breast or lumpectomy and radiation are the most common forms of treatment. But wide excision of the tumor - without radiation - cures just as many patents. This was proven by the well known US Lumpectomy Study. The Texas Cancer Center encourages this limited surgery in selected patients who are unable to have radiation treatment. Additional medical research supporting our recommendations can be found in our "Medical Research" section. Most of this research is directly linked to the National Library of Medicine. There are no medical studies which refute this conservative treatment strategy.

    INTRODUCTION

    Breast cancer is the most common cancer among women. It affects about one out of every nine females at some time during life. In the United States, about 175,000 women each year are diagnosed with breast cancer; about 45,000 of them die of this disease. The diagnosis of breast cancer has been increasing during the past several years, primarily due to earlier detection with the increasing use of mammography. No cancer has been more thoroughly studied than breast cancer. I believe that some of
    the biological lessons learned from this disease can be applied to other solid tumors.

    (Return to Top)

    STAGES OF DISEASE

    Today there are two principle staging systems used for breast cancer: (1) the TNM system, and (2) the traditional staging system.

    The TNM Staging System

    The TNM staging system is a popular staging system, which has been developed over that past forty years. It was developed by the Union Internationale Contra Cancer (UICC) [The International Union against Cancer], an organization located in Europe. It is based upon: (1) the greatest diameter of the tumor [T], (2) the involvement of regional lymph nodes [N], and (3) the presence or absence of distant metastases [M]. The TNM system is particularly useful in scientific studies, because patients can be studied and compared in precisely defined groups. The TNM system is complex and is difficult to use by practicing physicians, because there are dozens of different combinations of the various T, N, and M numbers. This is a simplified summary of the system.

    T Primary Tumor

    T1 Tumor is less than or equal to 2 cm.

    T2 Tumor is less than or equal to 5 cm.

    T3 Tumor is greater than 5 cm.

    T4 Tumor with direct extension to the chest wall or skin.

    N Regional Lymph Nodes

    N0 No cancer is present in the lymph nodes.

    N1 Lymph nodes contain cancer.

    N2 Lymph nodes are large and fixed together or to nearby tissue.

    N3 Lymph nodes near the collar bone are involved.

    M Distant Metastasis

    M0 No distant metastases

    M1 Distant metastases are present.

    The Traditional System

    This system has developed over of the past sixty years, and is popular among most practicing physicians in the United States.

    Stage 0 - Carcinoma in situ. There is no invasion or spread of disease. The five-year survival rate is over 90%.

    Stage I - A tumor which is two centimeters or less in diameter with no evidence of spread to the lymph nodes or distant organs. The five-year survival rate is about 85%. (T1, N0, M0)

    Stage II The tumor is five centimeters or less in diameter or the patient has positive lymph nodes in the axilla. The five-year survival rate is about 60%. (T2, N0, M0; T02, N1, M0; T3, N02, M0)

    Stage III - The tumor mass is larger than five centimeters in diameter, or there are positive lymph nodes, which are fixed to other tissue. The lymph nodes may be adherent to one another or to the underlying muscle or overlying skin. The five-year survival rate is about 40%. (T04, N03, M0 excluding those combinations listed above.)

    Stage IV - The tumor is fixed to the skin or chest wall, or there is lymph node spread above the collar bone, or there are distant metastases already present. The five-year survival rate is less than 10%. (T04, N03, M1)

    These stages are based upon clinical evaluation. The doctor feels the tumor and estimates its size. He examines the patient for enlarged lymph nodes in the axilla. If he finds them he estimates whether they feel malignant. This is called clinical staging.

    After surgery more accurate information may be obtained. Staging which is based upon microscopic examination of both the tumor and the lymph nodes by a pathologist is called pathological staging. Consider a patient who has a 1.5 centimeter tumor in the right breast with no enlarged lymph nodes. After surgery the pathologist finds microscopic cancer in three of her lymph nodes. The patient was initially clinical stage I. After surgery she would be classified as pathological stage II.

    (Return to Top)

    TYPES OF TREATMENT

    Surgery and radiation therapy are the primary forms of treatment for breast cancer, as they have been for most of this century. Chemotherapy and biological therapy are promising additions to the armamentarium, but there effects thus far are limited.

    Surgery

    Radical Mastectomy - Breast cancer has traditionally been treated with removal of the entire breast, the lymph nodes in the arm pit, and the muscles beneath the breast (pectoral muscles). This combination of procedures is called the radical mastectomy or the Halsted radical mastectomy, named after William Halsted who developed and popularized the operation (see Chapter 1, page ). The radical mastectomy concludes with skin lying on top of ribs, giving a "washboard" appearance to the chest.

    Modified Radical Mastectomy - This operation is like the radical mastectomy except the muscles beneath the breast are not removed. This gives the patient a smooth chest.

    Breast-sparing Surgery - All surgeons agree that patients with stage I and II breast cancer should have their entire tumor completely removed. This is called tumor excision, a general term that does not specify the amount of tissue that is removed. These procedures have more precise definitions:

    Lumpectomy - Removal of the cancer without a wide margin of normal tissue. Some edges of the tumor are usually checked by a pathologist to be sure there is no tumor. In the NSABP lumpectomy study [B06] over 40% of patients treated with lumpectomy without radiation therapy developed local recurrence. This is the least aggressive type of tumor excision.

    Wide excision - This is a general term which means removal of the tumor together with an undefined "wide" margin, usually at least 1 cm, of normal tissue.

    Partial Mastectomy - Excision of the entire tumor with a wider margin of breast tissue. The goal is usually a 2 cm margin. The removal of the tumor and a surrounding margin of tissue creates a defect or hole in the breast. Surgeons have traditionally closed this hole by sewing the remaining breast tissue to itself. The NSABP trial determined that surgeons could sew together only the skin of the breast. This allows the cavity in the breast to fill with lymph fluid, which eventually becomes soft scar tissue. This technique create a more normal appearing breast. It was practiced for decades by the late Peyton Barnes, Sr. of St. Joseph Hospital in Houston.

    Quadrantectomy - Excision of an entire quarter of the breast surrounding the tumor.

    Axillary Dissection - This is an operation, which removes the lymph nodes in the axilla. It is usually done together with a breast sparing operation. The lymph nodes are removed to learn the extent of tumor spread. This is a procedure that determines the stage of disease and may influence the use of additional (adjuvant) therapy such as chemotherapy or Tamoxifen.

    Sentinel Node Biopsy - A dye is used to identify only those nodes to which a cancer is likely to spread. The surgeon only removes those 3 or 4 nodes and checks them for cancer. If they are free of cancer cells, no more surgery is required.

    Radiation Therapy

    Radiation therapy is used to eradicate microscopic cells that might remain after surgery. It is no longer used following modified radical mastectomy even for patients with stage II disease. Radiation can reduce local recurrence with some patients, but it does not increase survival. Following breast conserving surgery, radiation is usually administered to the remaining breast tissue, sometimes with a dose of radiation concentrated on the tumor site. It is given five days per week for five to six weeks.

    Chemotherapy

    Patients with cancer in their lymph nodes (Stage II) may benefit from adjuvant chemotherapy. Premenopausal women are sometimes treated with a combination of three to five drugs. Treated women may have as much as a 7% better chance of surviving five years than untreated women. However, other specialists believe that the survival benefit is not this great. Barber Mueller of the McMaster University in Hamilton, Ontario is one of them. He argues that about 6% of women have their lives prolonged by about 14 months. The treatment does cause side effects, like hair loss, nausea, and vomiting. The number of months of misery is probably as important a consideration as the number of months of added survival. Some oncologists base their decision to use chemotherapy upon the presence or absence of risk factors present, e.g., tumor size, estrogen receptor status, DNA studies, etc.

    Studies show that postmenopausal women are less likely to benefit from multidrug adjuvant chemotherapy. Those who do benefit are estrogen receptor negative. Patients with estrogen receptor positive tumors usually benefit from tamoxifen given for two to five years. Women with stage II cancer improve their chances of surviving five years by about 6%. Tamoxifen may also benefit patients with stage I cancer (negative lymph nodes). The side effects of tamoxifen are much less than those of conventional chemotherapy, but can include hot flashes, nausea and vomiting. Dosage adjustments can sometimes reduce these symptoms. Some physicians suggest chemotherapy for selected patients with negative lymph nodes.

    Multidrug chemotherapy is able to cure some patients with advanced, localized breast cancer. The most aggressive form, known as inflammatory breast cancer, was once fatal in 95% of patients within one year. Now as many as 50% are living ten years or longer.

    (Return to Top)

    TCC ANALYSIS

    Breast-sparing surgery is the treatment of choice for most patients with early breast cancer. Unfortunately many patients still elect to have a mastectomy, because they are not able to undergo several weeks of radiation treatment. Others choose mastectomy because they feared local recurrence. Today fewer than half of patients with early breast cancer are being treated with breast-sparing techniques.

    Several studies have shown that a patient's decision to have a mastectomy is influenced by the preference of the surgeon toward more radical treatment. Now the debate should focus on the routine use of radiation therapy following partial mastectomy. In June 1990 a group of medical specialists, researchers, a nurse and lay female met at the National Institutes of Health. This Consensus Development Conference on the Treatment of Early Stage Breast Cancer concluded, "Although local control can be obtained in some patients with local excision alone, no subgroups have been identified in which radiation therapy can be
    avoided." This recommendation says that all patients who have breast-sparing treatment should receive postoperative radiation therapy. I do not agree with this recommendation. It reflects a disadvantage of the consensus conferences its goal of a single therapy on which most or all of the participants agree. This conference should have offered a range of alternatives (practice parameters), which consider the wishes of the patient and the opinion of the treating physician.

    In 1992, the American College of Radiology, the American College of Surgeons, the College of American Pathologists and the Society of Surgical Oncology published "Standards for Breast Conservation Treatment." This twenty page paper also strongly emphasizes the role of radiation therapy. The last section is entitles, "Area for Further Research." Among the eleven questions is, "Are there patients for whom breast irradiation can be omitted?" The implied answer is," Today, none." The paper has 43 references in the bibliography. Chapters 7 and 18 of this book include several studies which recommend partial mastectomy alone for selected patients with early breast cancer. None of these papers is included in the bibliography of the paper from the American College of Radiology.

    In England over one third of surgeons treat their patients with wide tumor excision without postoperative radiation therapy. I believe that many patients with stage I cancer can be spared postoperative radiation therapy. Radiation does reduce local recurrence following narrow excision, but it does not add a single day to the survival of patients with breast cancer. Local recurrence can be minimized by surgery alone. I believe that recent experience shows that surgeons who perform a careful partial mastectomy can achieve results equal to those achieved by lumpectomy and radiation therapy. Surgeons in England, Sweden and Canada have achieved local recurrence rates of 10 - 11% with surgery alone. In this country surgeons at the Cleveland Clinic, the Roswell Park Cancer Institute, and the University of Miami have achieved similar results with meticulous surgical techniques.,,

    Reexcision of this cancer does not impair survival. There are several factors that influence recurrence rates after surgery: the size of the primary tumor, the margins of excision (both width and pathological status), the lymph node status, patient age, the presence of intraductal carcinoma, tumor grade, DNA analysis, and invasion of tumor into blood vessels, nerves or lymphatic vessels. As the number of adverse factors increases, the chances for local recurrence and/or distant spread also increase. If patients are carefully selected based upon these factors, satisfactory local control can be achieved with surgery alone.

    (Return to Top)

    TREATMENT OPTIONS

    The treatment of breast cancer has been changing significantly in the United States. Breast sparing surgery is widely practiced. Reconstructive procedures have improved markedly. Radiation techniques have changed to increase the local effectiveness and reduce complications.

    Stage I - A tumor of 2 cm or less without spread to the axillary lymph nodes.

    I believe that stage I patients can prudently decline postoperative radiation therapy, if the tumor can be excised with a one to two cm margin of normal tissue, while preserving a cosmetically acceptable breast. The margin is influenced by the tumor size compared to the breast size. The surgeon must balance the functional loss and cosmetic defect of the surgery against the risk of recurrent cancer. To underline an important point: If local recurrence were a great survival hazard, then the added security of radiation might be justified. But the NSABP lumpectomy trial [B06] proved that postoperative radiation therapy does not improve survival. In short, recurrent disease can be safely excised without compromising patient survival. Excision alone spares patients the five weeks of daily radiation therapy and its unpleasant side effects, as well as the possible long term complications of radiation. Each area of the body can only tolerate a limited quantity of radiation. Once that level has been reached more radiation is seldom given. Thus, it may be prudent to keep this therapy in reserve.

    Removal of the lymph nodes under the arm (a staging axillary dissection) may be performed, if the results affect subsequent therapy. Most patients with tumor 1 cm or smaller can prudently decline axillary dissection, since more than 95% of these patients have an excellent prognosis without adjuvant treatment. A postmenopausal patient may elect to take tamoxifen, whatever the lymph node status. This is another reason to avoid an axillary dissection. A premenopausal patient with a 2 cm tumor may elect to receive adjuvant chemotherapy, if the lymph nodes are positive. Therefore, the surgeon may perform an axillary dissection after the tumor has been thoroughly tested.

    Stage II - A tumor of 5 cm or less with or without spread to the axillary lymph nodes.

    Wide tumor excision and axillary dissection with radiation therapy is becoming standard therapy in most patients. If the surgeon is able to remove a wide margin of healthy tissue, radiation therapy may be omitted in selected patients. If the patient has a tumor, which is large compared with the size of the breast, she may achieve better cosmetic results with mastectomy. Tamoxifen is given to some postmenopausal patients with estrogen receptor positive tumors. Combination chemotherapy may be appropriate for premenopausal women.

    Stage III - The tumor mass is larger than 5 cm or the axillary lymph nodes are fixed to one another or to surrounding tissue.

    Preoperative chemotherapy followed by partial mastectomy or modified radical mastectomy. Postoperative radiation therapy may reduce local recurrence. Postoperative chemotherapy may also be used.

    Stage IV - There are positive lymph nodes above the collar bone or distant metastases.

    Treatment recommendations are the same at for Stage III.

    SPECIAL CONSIDERATIONS

    Some surgeons consider partial mastectomy to be unacceptable or less acceptable under the following circumstances:

    1. The tumor is too large (greater than 5 cm) or relatively large compared to the size of the breast.

    If the surgeon can remove the tumor and leave a cosmetically acceptable breast, conservative surgery may be possible. Investigators at M. D. Anderson Hospital have treated patients with large tumors over five centimeters in diameter using preoperative chemotherapy and breast conserving surgery. If breast preservation is reasonable for patients with 5 cm tumors or stage III disease, it should be prudent for many patients with less advanced disease.

    2. There is extensive intraductal cancer (EIC) throughout the breast.

    Many studies have shown that patients with EIC are at a greater risk of developing local recurrence, especially if they are not treated with radiation therapy. Patients with this finding should receive radiation following a partial mastectomy.

    3. The tumor location is unsuitable, e.g., beneath the nipple.

    It is more difficult to obtain a good cosmetic result if the tumor is beneath the nipple. If the tumor itself is directly against the nipple, the nipple itself may need to be excised. In special cases you and your doctor might elect to save the nipple and rely on radiation therapy to kill a few remaining tumor cells.

    4. There is more than one tumor.

    Two or more tumors can be excised separately. Again the important consideration is removal of all the cancerous tissue.

    5. The cancer is in situ.

    In situ cancer is very early disease. It has not yet begun to invade into locally surrounding tissues. But some investigators have found patients with this disease to have a higher incidence of multiple small cancers in the breast. In situ cancers have been studied in an NSABP trial. Fisher et al. concluded that radiation therapy reduced the rate of local recurrence following lumpectomy, did not improve survival. (See below, "Medical Research since 1995.")

    (Return to Top)

    MEDICAL RESEARCH

    The history of breast cancer treatment can be found on www.cancerebook.com in Chapter 1. Beginning with the radical mastectomy of Halsted, it reviews the studies, which have led some surgeons to practice tumor excision plus post-operative radiation therapy. But, during the late 1980's, 55% to 90% of patients with stage I disease elected to have a mastectomy. (1),(2) Some patients did not wish to undergo several weeks of radiation treatment, or they found that radiation facilities were not easily available.(3) Others chose mastectomy because they feared local recurrence. This is the reason that most surgeons recommend the routine use of postoperative radiation therapy following any form of tumor excision. In Chapter 4 I tried to reassure you that local recurrence following conservative surgery -- local persistence -- is not a grave event. Reexcision of a locally persistent cancer does not impair survival. In this chapter I would like to examine the role that radiation therapy plays in breast-sparing surgery, and encourage selected patients to avoid radiation altogether.

      In the United States, the NSABP lumpectomy trial [B-06] is largely responsible for the increasing popularity of breast-conserving surgery.(4) This study proved that lumpectomy or lumpectomy plus radiation therapy can achieve survival rates which are equal to mastectomy for patients with stages I and II breast cancer. The study also showed that patients treated with lumpectomy alone have a very high rate of local recurrence. These results are summarized in Table I.

      Lumpectomy alone (without radiation therapy) resulted in a high rate of local recurrence, because lumpectomy removed such a narrow margin of breast tissue, usually less than 1 cm. Most breast cancers send out strands of tumor cells in many directions. Tumor cells grow along these strands.

      In the NSABP trial most patients had a tumor excision that was close to the tumor, within 1 cm. Although the primary mass was removed, in many patients some cancer cells remained along these strands. There were so few cells that they could easily be missed, even by a careful surgeon and pathologist.

      I believe that the secret to successful surgery is wide margin of excision. Excision of a 1 - 2 cm margin of breast tissue can remove most or call of the breast cancer cells in the breast. There is no doubt that radiation therapy killed tumor cells in most of the patients treated by lumpectomy and radiation. It reduced local recurrence from 43% to 12%. That is dramatic. But, can these cells be eliminated by surgery alone?

     I believe that recent experience shows that surgeons who perform a careful wide excision, a real partial mastectomy, can achieve results equal to those achieved by lumpectomy and radiation therapy. In this section I will focus on the experience of those surgeons who have treated patients with breast-sparing surgery alone. I have included the results of the NSABP study primarily for comparison.

      In 1939, Vera Peters of the Princess Margaret Hospital in Toronto began to treat patients with tumor excision.(5) By 1974, she had treated 184 patients with excision and postoperative radiation therapy and 19 patients with excision alone. Only one of the 19 patients developed "progressive disease." The survival rates in these two groups were the same. More recent results from this institution are presented in Table II.

      George Crile of the Cleveland Clinic began treating patients with partial mastectomy in 1955. About 20% of his patients, those with more advanced disease, received postoperative radiation therapy.(6) In 1990, he reviewed his experience with 291 patients treated through 1975.(7) Thirty-two patients (11%) developed local recurrence in the breast.

      In 1993, the Cleveland Clinic reported its experience treating 328 patients with lesions 2 cm or less in diameter. Following partial mastectomy about 11% of stage I patients developed local recurrence after five years; 14% of these patients developed local recurrence after 10 years.(8) The importance of wide margins is demonstrated in the results from the Cleveland Clinic, where margins of 1 - 2 cm were standard. The Cleveland Clinic practices a meticulous technique, which Crile originally called a partial mastectomy.

      In 1971, Robin Tagart of the Newmarket General Hospital in England began to treat 37 patients with partial mastectomy without postoperative radiation. He ended his study in 1978, when he learned that 37% of patients had developed local recurrence in the treated breast.(9) But, he concluded that primary treatment of breast cancer did not affect survival even when limited to partial mastectomy alone.

      Several institutions have recently reported their experience with breast-conserving surgery without radiation therapy.(10),(11) All agree that survival is not adversely affected by the omission of radiation therapy. The primary question then becomes what is the chance of developing local recurrence if radiation is omitted?

    Is Radiation Always Necessary?

      I will now focus on patients who have tumors, which are 2 cm or less in diameter. Table II presents the experience of several institutions treating patients with tumor, which are 2 cm or less in diameter. Most breast cancer patients in the United States are now treated with tumors of this size. Larger tumors are much more difficult to adequately treat using surgery alone. Patients with tumors larger than 2 cm are much more likely to develop local recurrence (22% - 35%).

      These studies show that patients whose tumors can be removed with a 1 - 2 cm margin of tissue can often be spared postoperative radiation therapy. Local recurrence rates of 11% or less can be achieved in patients with tumors of 2 cm or less and negative axillary nodes. Most of these institutions no longer recommend routine radiation therapy following breast-conserving surgery. Physicians at the Royal Marsden Hospital, the Uppsala-Orebro Hospital, the University of Miami, Roswell Park Memorial Institute, and the Cleveland Clinic believe that radiation therapy can be safely eliminated in selected patients. There is nearly complete agreement that lymph nodes should be free of disease, and there should be little or no evidence of surrounding cancer (multicentricity, intraductal disease, or carcinoma in situ).

    Treatment

    Local        Recurrence

    Survival Rate after 8 years

    Mastectomy

    8%

    82%

    Lumpectomy alone

    43%

    83%

    Lumpectomy with radiation

    12%

    84%



    Table I - Local Recurrence and Survival in the NSABP Lumpectomy Trial [B-06] 4,(12)



    Trial

    Number of Patients

    Margins

    Rate of Recurrence

    Royal Marsden(13)

    81

     2.5 cm

    11%(15)

    Uppsala-Orebro(16)

    194

     1 cm

    10%

    Cleveland          1957 - 1975(17),(18)

    152

     2 cm

    11%

    Roswell Park(19)

    78

    1 - 2 cm

    13%

    Miami(20)

    59

     1 cm

    10%

    NSABP(21)

    298

    <1 cm

    27%

    Princess Margaret(22)

    207 - (23)

    0.5 - 1 cm

    14% -low risk

    Cleveland 1975-1988(24)

    328

     2 cm

    11%

    Milan, Italy(25)

    280

    2 - 3 cm

    9%

    Table II - Patients with tumors 2 cm.

      Investigators at Royal Marsden Hospital recommended that patients less than 50 years of age should be treated with radiation therapy. Investigators from Roswell Park Memorial Institute recommended radiation therapy for patients less than 70 years of age. Recurrence is less common among older patients. Surgeons from the University of Miami use postoperative radiation therapy if the tumor invades into nerves or lymph or blood vessels.

      There are several factors that influence recurrence rates after surgery: the size of the primary tumor, the margins of excision (both width and pathological status), the lymph node status, patient age, the presence of intraductal carcinoma, tumor grade, DNA analysis, and invasion of tumor into blood vessels, nerves or lymphatic vessels. If patients are carefully selected patients based upon these factors, satisfactory local control can be achieved with surgery alone.
     

    1. Lazovich D, White E, Thomas DB, Moe RE. Underutilization of breast-conserving surgery and radiation therapy among women with stage I or II breast cancer. JAMA 1991;266:3433-3438.

    2. Osteen RT, Steele, Jr. JD, Menck HR, Winchester WP. Regional differences in surgical management of breast cancer. CA 1992;42:39-43.

    3. Tate PS, McGee EM, Hopkins SF, Rogers EL, Page GV. Breast conservation versus mastectomy: patients preferences in a community practice in Kentucky. J Surg Oncol 1993;52:213-226.

    4. Fisher B, Redmond C, Poisson R, et al. Eight-year 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;320:822-828.

    5. Peters MV. Wedge resection with or without radiation in early breast cancer. Int J Radiation Oncology Biol Phys 1977; 2:1151-6.

    6. Crile Jr G, Cooperman A, Esselstyn Jr CB, Hermann RE. Results of partial mastectomy in 173 patients followed for from five to 10 years. Surg Gynecol Obstet 1980; 150:563-566.

    7. Crile Jr G, Esselstyn Jr CB. Factors influencing local recurrence of cancer after partial mastectomy. Cleve Clin J Med 1990; 57:143-6.

    8. Esselstyn CB. A technique for partial mastectomy. Surg Clinic North Am 1975;55:1065-1074.

    9. Tagart R, Brather D, Hartley L, Sikora K. Partial mastectomy alone in early breast cancer. Brit Med J 1985; 290:434.

    10.  Reed MWR, Morrison JM. Wide local excision as the sole primarily treatment in elderly patients with carcinoma of the breast. Br J Surg 1989;76:898-900.

    11.  Hermann RE, Grundfest-Broniatowski S, Esselstyn CB. Breast-conserving surgery: how much is enough? Sem Surg Oncol 1992;8:136-139.

    12.  Fisher B, Wickerham DL, Deutsch M, Anderson S, Redmond C, Fisher ER. Breast tumor recurrence following lumpectomy with and without breast irradiation: an overview of recent NSABP findings. Sem Surg Oncol 1992; 8:153-160.

    13.  Greening WP, Montgomery ACV, Gordon AB, Gowing NFC. Quadrantic excision and axillary node dissection without radiation therapy: the long-term results of a selective policy in the treatment of stage I breast cancer. Eur J Surg Oncol 1988;14:221-225.

    15.  Includes axillary recurrences.

    16.  THE UPPSALA-OREBRO BREAST CANCER STUDY GROUP. Sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J natl Cancer Inst 1990;82:277-282.

    17.  Hermann RE, Esselstyn CB, Crile G Jr, et al. Results of conservative operations fro breast cancer. Arch Surg 1985; 120:746-751.

    18.  Crile G Jr, Esselstyn CB Jr. Factors influencing local recurrence of cancer after partial mastectomy. Cleve Clin J Med 1990; 57:143-6.

    19.  Nemoto T, Patel LK, Rosner D, Dao TL, Schuh M, Penetrante R. Factors affecting recurrence in lumpectomy without irradiation for breast cancer. Cancer 1991;67:2079-2082.

    20. Moffat FL, Ketcham AS. Breast-conserving surgery and selective adjuvant therapy for stage I and II breast cancer. Sem Surg Oncol 1992;8:172-176.

    21.  Fisher B, Anderson S, Bryant J et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233-1241.

    22.  Clark RM, McCulloch PB, Levine MN, Lipa RH, Wilkinson RH, Mahoney LJ, et al. Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer. J Natl Cancer Inst 1992;84:683-689.

    23.  Tumors 2 cm and pts 50 years of age.

    24.  Hermann RE, Esselstyn CB Jr, Grundfest-Broniatowski S, et al. Partial mastectomy without radiation is adequate treatment for patients with stages 0 and I carcinoma of the breast. Surg Gynecol Obstet 1993; 177:247-53.

    25. Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. New Engl J Med 1993; 328:1587-91.

    Medical Research since 1995

    The most significant research on conservative surgery for invasive breast cancer was published prior to 1995. It proved that conservative surgery and radiation therapy is safe and effective treatment. In 1990, the National Institutes of Health recommended that all patients treated with lumpectomy should have postoperative radiation. This remains standard practice in the U.S. Today doctors are trying to determine if postoperative radiation therapy prolongs the lives of any patients. If it does, precisely which patients benefit? As I have repeatedly stated, there is no evidence that adjuvant radiation therapy prolongs the lives of women with early breast cancer.

    The Effects of Radiation Therapy

    In 2000, a group of British physicians reviewed 40 different scientific studies to determine the risks and benefits of radiation therapy.(1) They reviewed the treatment of 20,000 women treated with either mastectomy or breast-sparing surgery. They found that radiation reduced local recurrence at 10 years from about 30 percent to about 10 percent. But, radiation therapy had little effect on overall survival. After 20 years the "survival was 37.1 % with radiotherapy versus 35.9%" without. The investigators explained that the radiation techniques used decades ago caused damage to the heart. They concluded that modern radiation techniques should increase the overall survival rate at 20 years by 2 - 4 percent.

    The effect of radiotherapy on survival is very controversial and very complex. A slight survival benefit of radiation therapy has been reported in some patients with stage II and III breast cancer. For many years I have suggested that radiation therapists should attempt to precisely show how their treatment effects survival. Do some unirradiated patients develop local recurrences which are difficult to find, e.g., high in the arm pit or under the breast bone? Do some recurrences grow to a large size? Could the spread of tumor cells from these recurrences have been prevented by better surgery - either initially or later? C.D. Atkins of New York correctly observed that radiation therapy was of little survival benefit to patients who had adequate surgical treatment.(2) And the British investigators agreed with Atkins.

    It is generally recognized, that despite the large mass of information available, many important questions remain to be answered. Thus far, the mass of information is compatible with the principle thesis of the Texas Cancer Center: Locally recurrent cancer does not become a threat to survival unless it exceeds the volume of the primary tumor.

    Partial Mastectomy Without Radiation

    This topic was covered in Appendix I. Since 1995, additional studies have supported the selective elimination of radiotherapy following breast-sparing surgery. J. de Csepel and associates of Mount Sinai Medical Center in New York studied 43 patients who did not receive radiotherapy.(3) They concluded that some elderly patients, those with other diseases and those with metastatic cancer could decline radiotherapy. Investigators in Austria and Australia have recently eliminated radiation therapy from the treatment of selected, elderly patients.(4), (5) They agree that breast-sparing surgery and tamoxifen are sufficient for some patients.

    Ductal Carcinoma In Situ (DCIS)

    Most of the recent significant progress in breast cancer research has occurred among patients with ductal carcinoma in situ (DCIS). DCIS is an initial step in a process that leads to invasive breast cancer. Until recently, mastectomy was the most common form of treatment. But, lumpectomy with radiation therapy has become an accepted alternative. As stated on page 138, radiation therapy reduces the rate of local recurrence without increasing survival. This important principle applies to both invasive breast cancer and DCIS, as well. Some surgeons are now eliminating radiation from the treatment of selected patients. The selection of these patients is largely determined by three important prognostic criteria: 1) tumor size, 2) tumor grade, and 3) the margin of excision. These criteria have been combined into the Van Nuys Prognostic Index (VNPI). Consider these important factors as you read the studies below.

    In 1998, B.F. Fisher and the NSABP investigators published the 8-year results of their B-17 trial.(6) About 400 women with DCIS were treated with lumpectomy only. Most of the tumors were smaller than 2 cm. When pathologists examined the cut edges of the tissue removed by the surgeons, they found no tumor cells. But, as in the earlier NSABP lumpectomy trial for invasive breast cancer (B-06), the margins of excision were narrow. (The significance of margins is discussed in Appendix I.) Within eight years after treatment two types of recurrences developed. Some patients (about 12 percent) developed additional DCIS; some patients (also about 12 percent) developed invasive breast cancer.

    A second group of about 400 patients was randomly assigned to receive lumpectomy followed by radiation therapy. Radiation had its greatest effect in reducing invasive recurrences - from about 12 percent to about 4 percent. Radiation also reduced the number of noninvasive recurrences (DCIS) from about 12 percent to about 8 percent. Again, radiation therapy did not improve survival.

    Now consider some more precise numbers. Of 403 women treated with lumpectomy alone, there were 53 invasive recurrences and 51 noninvasive recurrences. Only one of these women died of breast cancer. That is 1 death, that might have been prevented by radiation, out of 403 women treated with lumpectomy alone. (The 3 other deaths in this group could not have been prevented by radiation, since these 3 women did not develop a local recurrence.) Of the 411 women treated with lumpectomy and radiation, two patients died following a local recurrence - twice the number as in the radiation-free group.

    Among the entire group of 814 women, most of the breast cancer deaths (8 of 14) occurred in women who developed metastatic disease without having a recurrence in the breast. Two patients died from cancer in the opposite breast. Only 3 patients died following a recurrence in the treated breast.

    Among the patients who received no radiation there were four deaths attributable to breast cancer. Among those who received radiation there were 10 deaths attributable to breast cancer - a 2 1/2 fold difference. According to my calculations this difference comes within 1 percent of being statistically significant. Yet, the NSABP investigators did not call attention to these results. It is clear that radiation therapy did not improve the survival of patients in this study. In fact, the results suggest that more patients may have died of breast cancer if they received radiation.

    Another NSABP trial (B-24), demonstrated that among patients treated with lumpectomy and radiation, the addition of tamoxifen reduces the incidence of all breast cancer recurrences from 13.4 percent to 8.4 percent, but there was no survival benefit.(7) M.J. Silverstein and associates from the University of Southern California studied 133 patients whose DCIS had been excised with a margin of 1 cm or more.(8) They concluded that these patients did not need postoperative radiation therapy. In April, 1999, the Consensus Conference on the Treatment of In Situ Ductal Carcinoma of the Breast was held in Philadelphia.(9) This group concluded that invasive carcinoma of the breast develops each year in about 1 percent or less of patients treated with local excision - with or without radiation. There was no general agreement on the optimal form of treatment, but many panelist considered wide excision alone (1 cm margin or greater) to be acceptable. Some participants said that even patients with high grade lesions can be treated in this manner.

    Erroneous Conclusions about Radiation Therapy

    Most radiation therapists support the routine use of radiation after breast-sparing procedures. Recently, they have written over a dozen articles evaluating the threat of locally recurrent breast cancer.

    These articles follow a similar pattern. Investigators follow patients who were treated with breast-sparing surgery. They divide these patients into two groups - those who develop recurrent cancer in the treated breast and those who do not. The investigators observe that patients who remain free of local recurrence live longer than those who develop local recurrence. This is correct. They conclude that patients die from distant metastases caused by the recurrence. This is not correct. Even in the well-known NSABP lumpectomy trial, patients treated with lumpectomy alone, who then developed local recurrence, were 4.6 times as likely to develop distant metastases as those who remained free of local recurrence. But, the NSABP investigators concluded, correctly, that local recurrence was the indicator of a poor prognosis, but not its cause.

    Beginning on page 73, I try to explain these perplexing observations. In brief, there are two types of recurrence. Traditional local recurrence is a sign that the tumor has already spread. But, the persistence of tumor cells following conservative surgery (local persistence) is not a grave sign. Combining these two forms of recurrence leads to the confusing observations above. Following lumpectomy alone some patients developed traditional local recurrence. It was almost exclusively these patients, who developed distant metastases. (I also try to explain this confusing matter here in Appendix II. See Malignant Melanoma, Erroneous Conclusions.)

    B. Haffty and associates from Yale reported their experience with 973 patients treated with conservative surgery and radiation therapy.(10) They concluded, "Whether early breast tumor relapse is a marker for or cause of distant metastases remains a controversial and unresolved issue."

    Radiation therapists from the Hotel-Dieu de Quebec Hospital, Universite Laval reviewed the charts of 2,030 patients treated with breast-sparing surgery between 1969 and 1991.(11) At 10 years 13 percent of patients had developed local recurrence. Only 55 percent of these patients survived 10 years. Of patients who remained free of local disease, 75 percent survived ten years. The authors reported that the risk of distant metastasis was 5.1 times higher among patients with local recurrence. (As mentioned above, in the NSABP lumpectomy trial this figure was 4.6 times.) They concluded that local recurrence was the source of new distant metastases and the cause of death in some patients. This conclusion is incorrect.

    These investigators measured the size of the local recurrences. They found 27 patients had recurrences less than 1.5 cm in diameter; these patients had a 10-year survival of 72 percent. There were 94 patients who developed recurrences larger than 1.5 cm; they had a 10-year survival of 32 percent. Compare the 10-year survival of patients with small recurrences (72 percent) to that of patients with no recurrence (75 percent). This supports the many other studies which have proven that promptly-treated local recurrence does not spread. It also support my 1980 statement, "For instance, a patient who survives a carcinoma of 2 to 3 cm in diameter without developing distant metastases may be expected to survive a similar volume of tumor in adjacent breast or lymphatic tissue." (12)

    Of course, locally recurrent cancer can spread if it grows too large. Even today we do not know what "too large" means, because few investigators have measured the size of recurrences. For many years I have suggested that investigators should compare the size of each recurrence to the size of the primary (original) tumor. I believe that "too large" is any size which exceeds the size of the primary lesion.

    References since 1995

    1. Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomized trials. Lancet 355:1757-1770, 2000.

    2. Atkins CD. Breast cancer survival advantage with radiotherapy. Lancet 356:1269, 2000.

    3. De Csepel J, Tartter PI, Gajdos C. When not to give radiation therapy after breast conservation for breast cancer. J Surg Oncol 74:273-277, 2000.

    4. Gruenberger T, Gorlitzer M, Soliman T, Rudas M, Mittlboeck M, Gnant M, and others. It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients. Breast Cancer Res Treat 50:37-46, 1998.

    5. Sader C, Ingram D, Hastrich D. Management of breast cancer in the elderly by complete local excision and tamoxifen alone. Aust N Z J Surg 69:790-793, 1999.

    6. Fisher B, Dignam J, Wolmark N, Mamounas E, Costantino J, Redmond C, and others. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 16:441-452, 1998.

    7. Fisher B, Dignam J, Wolmark N, and others. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomized controlled trial. Lancet 353:1993-2000, 1999.

    8. Silverstein MJ, Lagios MS, Groshen S, Waisman JR, Lewinsky BS, Martino S, and others. The influence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med 340:1455-1461, 1999.

    9. Schwartz GF, Solin LJ, Olivotto IA, Ernster VL, Pressman PI. Consensus Conference on the Treatment of In Situ Ductal Carcinoma of the Breast, April 22-25, 1999. Cancer 88:946-954, 2000.

    10. Haffty BG, Reiss M, Beinfield M, Fischer D, Ward B, and McKhann C. Ipsilateral breast tumor recurrence as a predictor of distant disease: Implication for systemic therapy at the time of local relapse. J Clin Oncol 14:52-57, 1996.

    11. Fortin A, Larochelle M, Laverdiere J, Lavertu S, Tremblay D. Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy. J Clin Oncol 17:101-109, 1999.

    12. Evans RA. Host resistance to carcinoma of the breast. South Med J 73:1261-1263, 1980.

    (Return to Top)

     



Read about these cancers: bladder, breast, cervix, melanoma, prostate, rectum, and the soft tissue sarcomas. For other cancers, please call 713-975-8006 or e-mail the Texas Cancer Center.


Support the Texas Cancer Center

  The Texas Cancer Center gratefully welcomes contributions from all those
who would like to support our mission. Please make your check payable to
the Texas Cancer Center and mail it to 1011 Augusta Dr., Suite 210,
Houston, Texas 77057. The Texas Cancer Center is a 501 (c) (3)
organization and all donations are fully tax deductible.


If your donation is in memory or in honor of an individual, please give
us an appropriate name and address so we may acknowledge your gift. We
would like to publicly acknowledge all gifts. If you wish to remain
anonymous, please let us know.

more

Home | About Us | Understanding Cancer | Treatment Options | Consult Us | Donate