Radiation necessary in an early stage cancer

I sure don't want to leap into the fray with this thread. But I think the discussion might be more helpful if the phrase "early stage cancer" was been further clarified. There's a lot of difference between low grade DCIS and a stage 2 grade 3 with lymphovascular invasion. Yet both are sometimes called "early". I would suspect that we all could agree that the risk/benefit analysis would look quite different in these different cases. And I think we would also all agree that doctors should (and some of them do) look at each case individually when making recommendations for adjuvant treatment.

Actually MDB, I suspect my overall risk threshold is higher than yours.  I just don't see the point of taking stupid risks with life of the mother of my young children.  Nobody can tell my wife what her absolute risk is because nobody knows the chances of cancer cells remaining in her breast from her 1.3 cm, grade 2 tumor, after surgery.  All they know for sure is that the Pathologist did not detect anything in her lymph nodes.  And of course you are right.  We are all going to die someday of something.  So why worry about it.  Still when I drive, I wear my seat belt.  When I scuba-dive, I make sure my equipment, including pressure gauge and regulator are in good shape, when I ski, I sometimes where a helmet but still ski far faster than I should.  And when I daily trade stocks, I am sometimes as much gambling as investing, but its fun.

January 15, 2007

Predicting Recurrence

By Beth W. Orenstein

Radiology Today

Vol. 8 No. 1 P. 20

Researchers at Tufts_New England Medical Center are seeking a mathematical model to assess which women are likely to have their cancer return in an effort to safely spare some unnecessary radiation therapy.

Some women with early_stage breast cancer may only minimally benefit from radiation therapy, yet choosing who those patients are is clinically very difficult. Researchers at Tufts_New England Medical Center in Boston are working on a computer tool that may help solve this dilemma. The tool in development uses risk factors associated with breast cancer recurring in the same breast after breast_conserving surgery (BCS) to predict the likelihood of that happening.

Mona Sanghani, MD, lead author of the abstract, presented this work at the 48th annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) in Philadelphia in November 2006. Their paper was titled "Predicting the Risk of Local Recurrence in Patients With Breast Cancer: An Approach to a New Computer Based Predictive Tool."

"There are some patients who are at extremely low risk of the cancer coming back," Sanghani says. "This might help identify who those patients are."

Sanghani adds that when discussing treatment options with patients, physicians may feel more comfortable if they have such a tool. Also, the tool could help patients decide their course of treatment. "Maybe looking at more concrete numbers might help them decide one way or another," she says.

Even though the tool may be available online, Sanghani says, it is not intended for patients to make a decision on their own, but for them to use it when discussing the benefits of radiation treatment with their physicians.

According to the American Cancer Society, breast cancer is the most common type of cancer in American women. Every year, more than 210,000 women and 1,700 men are newly diagnosed with breast cancer.

If caught early, breast cancer can often be cured; approximately 80% of patients with breast cancer remain free of the disease 10 years after being diagnosed. Thanks to public education and proactive screening programs, small tumors are being found earlier in a greater percentage of women.

Breast cancers are considered early stage-stages 1 and 2-if they are not fixed to the skin or muscle. Also, if lymph nodes are involved, the nodes are not fixed to each other or to underlying structures.

Current Options

If the cancer is in its early stages when discovered, the current standard treatments are mastectomy or BCS followed by radiation therapy to kill any remaining cancer cells. External beam radiation therapy involves six to eight weeks of daily treatment. BCS is regarded as preferable to mastectomy and axillary dissection in most cases because studies have shown that survival rates are equivalent and BCS preserves the breast.

Standard breast_conservation therapy includes radiation therapy (typically external beam radiation, but sometimes brachytherapy procedures are used to shorten the radiation treatment) because studies have shown a higher recurrence rate in women who do not receive radiation. The Tufts studies compared randomized trials of women who had BCS with radiation therapy with randomized trials of women who had BCS without radiation therapy.

Radiation therapy has side effects. While most are manageable, Sanghani says, side effects can include fatigue, which often increases as the treatments progress. Also, changes and burns can occur in the breast skin and occasionally, and the breast can change color or size or can become permanently firm. Radiation therapy also increases the woman's risk of developing other cancers, such as soft tissue malignancies known as sarcomas. Sanghani says probably the biggest drawback of radiation therapy is that it is a significant investment of time for the patient.

Still, Sanghani adds, the researchers were not as concerned about avoiding the side effects of radiation, or the time for treatment, as they were about having women undergo the treatment when they would not necessarily benefit from it.

"We found that in speaking with people in the oncology community about it, it seems that patients are really walking the fine line as to attribution, whether or not they will get significant benefit from radiation therapy," Sanghani says. "The benefit does vary from person to person. So I think the tool will be most useful when you are looking at patients who are uncertain as to whether or not they want radiation and may be looking for data to back their choices."

Researchers developed the formula by looking at the following seven risk factors associated with recurrence in the same breast after BCS:

• patient age;
• margin status;
• lymphovascular invasion (LVI);
• tumor size;
• tumor grade;
• use of chemotherapy; and
• use of the drug tamoxifen.

Finding Key Variables

To study the risk factors, researchers reviewed all available randomized trials of BCS alone vs. BCS plus radiation therapy. They also reviewed meta_analyses and institutional reports. "We preferred to use randomized trials in breast_conserving therapy. However, we did include single institutions and retrospective trials if we felt like they added value to our knowledge," Sanghani says.

The studies had been published in the last 10 to 15 years, she says, and they had, on average, eight to 10 studies for each risk factor.

In the model, patient age groups are under the age of 40, then five_year increments up to the age of 70, and then age 70 and older. Margin status is: positive, 0 to 2 millimeters or greater than 2 millimeters. LVI is yes or no. Tumor size is less than 1 centimeter or greater than 1 centimeter. Tumor grade is low, intermediate, or high. Use of chemotherapy and use of tamoxifen is also yes or no.

Each risk factor was given a weight-the higher its importance in predicting recurrence, the higher it was weighted. "Then we combined all the risk factors in a mathematical model that we could use to predict the rate of recurrence for each patient," Sanghani says. When the patient's data is entered into the model, it predicts the likelihood of local recurrence within nine years.

For example, if a 48_year_old woman with a 1.8 centimeter, grade 2 tumor, with no LVI, margin status of 1 millimeter, who had chemotherapy and was taking tamoxifen and had radiation therapy, the model predicted a 7% chance of local recurrence with radiation therapy and a 36% chance without it. In that case, she would meet the benefit requirements. A second case is of a 75_year_old woman with a tumor size of 0.4 millimeters, grade 1 tumor, no LVI, margin status of 2 millimeters, no chemotherapy and no tamoxifen; the model predicted a local recurrence rate of 2% with radiation therapy and 8% without. That may be a case where the woman would not see a significant enough benefit to warrant undergoing radiation therapy.

Defining Additional Benefit

Sanghani says radiation oncologists like to see at least a 10% benefit from the therapy. "If the patient is only going to see a 2% to 3% benefit, it may not be an important treatment, and she may wish to consider not having it," she says.

The next step is to validate the study. "Now that we developed the model, it must be validated by independent clinical data. Only then can it be widely used," Sanghani says.

Carol L. Kornmehl, MD, FACRO, is a board_certified radiation oncologist at Passaic (N.J.) Beth Israel Regional Medical Center and author of The Best News About Radiation Therapy: How to Cope and Survive. She is also a clinical assistant professor of radiation oncology at Hahnemann University Hospital in Philadelphia.

Kornmehl believes that once the model is validated, it will become a valuable tool to radiation oncologists and their breast cancer patients.

"Once there is enough data-tens of thousands of women on the study-then we can have a comfort level with the tool," she says. "Until then, I think it would be premature to recommend not following BCS with radiation therapy."

Kornmehl expects it will take at least five to 10 years for the data to be acquired and of value. If cancer recurs in the same breast, it usually does so in two to three years, "but there can be recurrences after that," she says.

Because of that possibility, Kornmehl would like to see the data for five years and beyond. "If you have 10,000 women who are disease_free for a year, that doesn't mean anything; but if they are disease_free for 10 years, you would feel more comfortable recommending they might not want to undergo radiation therapy because the data would support that decision.

"I think I would feel comfortable saying to a patient, ‘We have 10_year data that suggests your risk factors are X, Y, and Z, and so the computer model shows chances of local recurrence without radiation therapy [are] slim, and you might consider not having it,'" she says.

Meanwhile, she says, she would not be comfortable recommending against follow_up radiation therapy. "I think the greatest risk is not taking one. Clearly, doing radiation is not a free lunch. It puts women at risk for other cancers later on, and there are other side effects. Also, it is inconvenient." However, the data that is currently available shows it is still the best course of treatment, Kornmehl says.

If the computer model proves that it can clearly identify the subset of women who are not likely to benefit from radiation therapy, then it could change standard practice, Kornmehl adds.

- Beth W. Orenstein is a freelance health writer and a regular contributor to Radiology Today. She writes from her home in Northampton, Pa.

Worried Hubby Posted this article:

"January 15, 2007

Predicting RecurrenceBy Beth W. Orenstein

Radiology Today"

Wow. Great article! As revkat said, thanks for posting it, I hadn't seen that one.  

Although, like revkat also said, it is unfortunate that we won't  have any official proof of anything, for years. But it's so encouraging that studies like this are in process. Maybe it will help my 19 year old daughter.

So, at this point, I truly believe that we all have to make decisions, for ourselves. Based on all available information. And it's VERY hard. Like I've said, I was so conflicted, I actually went to the Radiation SIM appt, before just walking out. Refused to sign the consent form. Everyone reading this knows what I'm talking about. 

I just could NOT DO IT. It felt so wrong, to me. This radiation. Based on everything that I'd read and everything that I knew, about my own body. And I felt so liberated, after walking out of there. Like this weight, had been lifted, off of me. I'd evaluated the risks, for me, and I did not want to do it. 

How old is your wife, worried hubby? You mentioned that you had young children, so she must be fairly young.

In any event, you've made the right choice, for you and your wife. As I have, for me.  

That is why discussions, like these, are so great. Like MarieKelley said, everyone is entitled to speak their mind. As long as it's done, respectfully.  And we're all civil, here. 

As I've said, I just had my BiRad1 mammo on both breasts, May, 2008. That is great, two years out, but still sweating this July CT.  For the Leio cancer. I think something is ... wrong. I can feel it. 

Yet, it is what it is. See what happens, July 23. 

Hi Marie, oh yes, and then, even when it is the accepted treatment, half the old coot docs/oncs won't change anyway!   The poor women caught in their net.  In Europe 70% of women have lumpectomies, and 30% have masts  (there are many very viable reasons for a mast) but here, the numbers are reversed, and no one seems to know why.

Sheesh, we truly do have to be our own informed consumers, and not be afraid to walk off.

mdb, what in the heck is your leio cancer?  Never heard of that one, but it doesn't sound like much fun.

Hugs, Shirl 

Hi all - definite changes with regards to radiation in early breast cancer.  Trials are on-going in Europe and the UK with intra-operative radiotherapy.  The entire treatment is done at the time of the operation - protection is given between the chest wall and the treatment area and the radiation dose is administered at the site of the tumour where it is most needed.  I had this done but, unfortunately, when I went for my post-op consultation the Consultant said that as I had DCIS in addition to the small 5mm tumour I would need external radiation also.  The protocol calls for this and allows for a reduced amount of external treatments (I had 15) and no boosts required.  Apparently the machinery needed for the intra-operative treatments is very expensive and the time in Theatre is extended quite a bit but the huge advantage is the reduced amount of radiation.

My hope is that the medical community will someday emphasize diet and exercise as a treatment for low grade tumors in situ like mine

We must live in separate universes.  For decades, in my universe, health experts have been preaching the virtues of a healthy diet and exercise for the prevention of disease.  Interestingly, a clinical trial showed that eating the right foods did not effect breast cancer.  Look it up at the National Cancer Institute if you happen to be in my universe anytime soon.

I remember the beta carotene craze!! It was going strong back at least 10 -15 years ago. Unfortunately, some people took it to the extreme. I remember a patient of mine who was convinced that beta carotene was the one thing that would cure his cancer. He took massive amounts of it. As I recall, he never actually refused conventional treatment, at least not initially, but he took in so much beta carotene that he eventually turned the color of a carrot.  He was VERY orange. I've seen lots of jaundice yellow from liver failure, but he was the first and last I've ever seen carrot orange.  It didn't help him at all, by the way - he died that same color, and I've sometimes wonder if he might have lived longer had he not done that.

Well, I'm not surprised that someone on the Johns Hopkins website would be promoting broccoliu sprouts since they've got a patent on them!! The call them "broccosprouts". Does that mean they make money off them?? Don't know. There were threads discussing them here a few years back.

Interesting study:

Clinical practice guidelines for the care and treatment of breast cancer:6. Breast radiotherapy after breast-conserving surgery (2003 update)

Timothy Whelan, Ivo Olivotto, Mark Levine, for the Steering Committee on Clinical Practice

Guidelines for the Care and Treatment of Breast Cancer*

Dr. Whelan is with the Cancer Care Ontario Hamilton Regional Cancer Centre and Associate

Professor in the Department of Medicine, McMaster University, Hamilton, Ont.; Dr. Olivotto

is with the BC Cancer Agency-Vancouver Island Centre and Clinical Professor in the

Department of Surgery, University of British Columbia, Vancouver, BC; and Dr. Levine is

Professor in the Departments of Clinical Epidemiology and Biostatistics and of Medicine and

is the Buffet Taylor Chair in Breast Cancer Research, McMaster University, Hamilton, Ont.

*The Steering Committee is part of Health Canada's Canadian Breast Cancer Initiative.

[Patient guidelines available here]

AbstractObjective: To help physicians and their patients arrive at optimal strategies for breast

radiation therapy after breast-conserving surgery (BCS) for early breast cancer.

Outcomes: Local control, survival, quality of life, adverse effects of irradiation and cosmetic

results.

Evidence: A literature search using MEDLINE from 1966 to October 2001 and

CANCERLIT from 1983 to September 2001. A nonsystematic review of the literature was

continued through April 2002.

Benefits: A decrease in local recurrence of breast cancer.Harms: Adverse effects of breast irradiation.Recommendations:

• Women who undergo BCS should be advised to have postoperative breast irradiation.

Omission of radiation therapy after BCS increases the risk of local recurrence.

• Contraindications to breast irradiation include pregnancy, previous breast irradiation

(including mantle irradiation for Hodgkin's disease) and inability to lie flat or to abduct

the arm. Scleroderma and systemic lupus erythematosus are relative contraindications.

• A number of different fractionation schedules for breast irradiation have been used.

Although the most common fractionation schedule in Canada to date has been 50 Gy in

25 fractions, recent data from a Canadian trial demonstrate that 42.5 Gy in 16 fractions

is as good as this more traditional schedule.

2

• Irradiation to the whole breast rather than partial breast irradiation is recommended.
• There is insufficient evidence to recommend breast irradiation with brachytherapy implants

or intraoperative radiation therapy. Further evaluation of these treatments in randomized

trials is required.

• Additional irradiation to the lumpectomy site (boost irradiation) reduces local

recurrence but can be associated with worse cosmesis compared with no boost. A boost

following breast irradiation may be considered in women at high risk of local

recurrence.

• Physicians should adhere to standard treatment regimens to minimize the adverse

effects of breast irradiation.

• When choices are being made between different treatment options, patients must be

made aware of the acute and late complications that can result from radiation therapy.

• Breast irradiation should be started as soon as possible after surgery and not later than

12 weeks after, except for patients in whom radiation therapy is preceded by

chemotherapy. However, the optimal interval between BCS and the start of irradiation

has not been defined.

• The optimal sequencing of chemotherapy and breast irradiation is not clearly defined

for patients who are also candidates for chemotherapy. Most centres favour the

administration of chemotherapy before radiation therapy. Selected chemotherapy

regimens are sometimes used concurrently with radiation therapy. There is no evidence

that concurrent treatment results in a better outcome, and there is an increased chance

of toxic effects, especially with anthracycline-containing regimens.

• Patients should be offered the opportunity to participate in clinical trials whenever

possible.

Validation: The original guideline was updated by a writing committee, which then

submitted it for review, revision and approval by the Steering Committee on Clinical Practice

Guidelines for the Care and Treatment of Breast Cancer. The current update did not undergo

an external review.

Sponsor: The Steering Committee on Clinical Practice Guidelines for the Care and

Treatment of Breast Cancer was convened by Health Canada.

Completion date: September 2002.

3

Approximately 80% of women who present with breast cancer have lesions that are amenable

to breast-conserving surgery (BCS). Randomized trials have shown that BCS is equivalent, in

terms of survival, to mastectomy (see guideline 3), and the use of BCS is increasing.

A number of well-executed clinical trials evaluating the role of breast irradiation after BCS

have been completed. These guidelines, which incorporate this information, are intended to

assist the patient and her physician(s) in making the most clinically effective and personally

acceptable choices concerning the use of breast irradiation after BCS for invasive breast

cancer. The management of ductal carcinoma in situ (DCIS) is addressed in a separate

guideline (guideline 5). The question of axillary node irradiation is not addressed in this

document.

Methods

The evidence reviewed for this document was retrieved through a systematic review of the

English-language literature using MEDLINE from 1966 to October 2001 and CANCERLIT

from 1983 to September 2001. Search terms included the following: "breast neoplasms,"

"segmental mastectomy," "lumpectomy," "breast conservation," "radiotherapy,"

"irradiation," "clinical trials," "practice guidelines" and "meta-analysis." Bibliographies from

recently published reviews were scanned and relevant articles retrieved. A nonsystematic

review of the literature and monitoring of major conferences on breast cancer were continued

through April 2002.

The quality of the evidence on which conclusions are based is categorized into 5 levels.1 The

initial draft of the original guideline was based on the report "Evidence based

recommendation report for breast irradiation following breast conserving surgery," prepared

for the Cancer Care Ontario Breast Disease Site Group. The iterative process used to develop

the original guideline has been described previously.2 A writing committee updated the

original guideline and then submitted it for further review, revision and approval by the

Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast

Cancer.

Recommendations (including evidence and rationale)The role of radiation therapy after BCS

• Women who undergo BCS should be advised to have postoperative breast

irradiation. Omission of radiation therapy after BCS increases the risk of localrecurrence.

There is substantial level I evidence that breast irradiation after BCS reduces the incidence of

local recurrence, providing a survival rate equivalent to that of mastectomy3-14 (Table 1).

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial, 2105

women with node-negative or node-positive breast cancer and tumours 4 cm or less in

diameter were randomly assigned to 1 of 3 treatment arms: (a) modified radical mastectomy,

(b) lumpectomy plus axillary dissection followed by local breast irradiation or (c)

4

lumpectomy and axillary dissection alone.3-5 There was no difference in survival between the

3 treatment groups at an average follow-up of 12 years.5 However, the rate of local recurrence

was substantially lower among all patients who received a lumpectomy plus local breast

irradiation of 50 Gy over 5 weeks to the whole breast than among patients who were treated

with lumpectomy alone (10% v. 35%, p < 0.001).5 For patients with node-negative disease

treated by lumpectomy, the rate of local recurrence among those who received adjuvant

radiation therapy was 12% compared with 32% among those who received no adjuvant

radiation therapy. For patients with node-positive disease (all of whom also received

chemotherapy), the rates of local recurrence with and without adjuvant radiation therapy were

5% and 41% respectively (level I evidence).

In another study, carried out in Sweden, 381 women with node-negative breast cancer and

primary tumours 2 cm or less in diameter were randomly assigned after sector resection to

receive either breast irradiation (54 Gy in 27 fractions to the whole breast) or no breast

irradiation.6-8 At 10 years' follow-up, the local recurrence rate was lower among those who

received irradiation than among those who did not (8.5% v. 24%, p = 0.0001) (level I

evidence).8 There was no difference in survival between the 2 treatment groups.

In a Canadian study, 837 patients with node-negative disease who underwent lumpectomy

were randomly assigned to receive either no breast irradiation or breast irradiation (40 Gy in

16 fractions over 3 weeks to the whole breast, plus a local boost of 12.5 Gy in 5 fractions

over 1 week to the primary site).9,10 The rate of local recurrence at a median of 7.6 years of

follow-up was 35% in the non-irradiated group compared with 11% in the irradiated group (p

< 0.001) (level I evidence).10 No difference in survival was detected between the 2 groups.

In an Italian trial, 567 women with either node-negative or node-positive tumours less than

2.5 cm in diameter were randomly assigned to undergo either quadrantectomy followed by

breast irradiation (50 Gy in 5 weeks to the whole breast, plus a boost to the tumour bed of 10

Gy in 5 fractions) or quadrantectomy without radiation therapy.11 At a median follow-up of 9

years the rates of local recurrence were 5.8% in the irradiated group and 23.5% in the nonirradiated

group (p < 0.001) (level I evidence). There was no difference in overall survival

between the 2 groups.12

In another trial, in Scotland, 585 women with primary breast cancers 4 cm or less in diameter

were randomly assigned after BCS and systemic therapy to receive either 50 Gy in 20 to 25

fractions to the breast with a boost to the tumour bed, or no radiation therapy.13 At 6 years,

local breast recurrence rates were much lower in the irradiated group than in the nonirradiated

group (5.8% v. 24.5%) (level I evidence). No difference was detected in survival

between the groups.

In a study conducted in Finland, 152 women over 40 years of age who had node-negative

breast tumours smaller than 2 cm in diameter were randomly assigned to lumpectomy alone

or to lumpectomy followed by radiation therapy (50 Gy in 5 weeks) to the ipsilateral breast.14

At 6.7 years of follow-up, the local recurrence rate was 7.5% in the irradiated group and

18.1% in the control group (p = 0.03) (level I evidence). There was no difference in overall 5-

year cancer-specific survival between the groups.

5

The 1995 update of the meta-analysis by the Early Breast Cancer Trialists' Collaborative Group

(EBCTCG) included 4 of the published trials and 2 unpublished trials involving over 4000

patients. The results are consistent with the findings of the 6 studies reported above. There was a

68% reduction in risk of local recurrence after radiation therapy but no significant impact on

overall survival (level I evidence).15 The EBCTCG met in the fall of 2000, and their updated

analysis should be available in the future.

In most of these trials, local relapse was treated by mastectomy despite a policy of re-excision

followed by breast irradiation for local relapse in patients treated by lumpectomy alone.6,9,11

The Swedish study6 reported an overall mastectomy rate for local recurrence of 70%, the

Canadian trial9 reported a mastectomy rate of approximately 50%, and the Italian study11

reported a mastectomy rate of 40%.

Are there any situations that confer so low a risk of recurrence that irradiation can safely be

omitted? The probability of local recurrence without radiation therapy is less when tumours

are small (< 2 cm in diameter) and when women are older than 50 years of age. However,

omission of irradiation after BCS increases the risk of local recurrence, even in these cases.

The Canadian study that evaluated the role of breast irradiation after lumpectomy in patients

with node-negative breast cancer found that women aged 50 years and older who had

tumours 2 cm or less in diameter were possibly a low-risk group.9 However, the rate of local

relapse among such women treated by lumpectomy alone was 22%.10 Similarly, in the

NSABP B-06 study, although tumour size predicted local recurrence in the breast, the risk of

recurrence after BCS among patients with node-negative disease with tumours 1 cm or less in

diameter who did not receive radiation therapy was still 25% (level III evidence).16 It has

been postulated that patients who undergo more extensive resection of the tumour my be at

somewhat lower risk of recurrence. However, the results of the Milan and Uppsala-Örebro

trials do not support this hypothesis. In the former trial, women who underwent

quadrantectomy without radiation therapy had a local recurrence rate of 23.5%.12 In the

Swedish trial, patients who underwent sector resection without radiation therapy had a rate of

24%.8

Investigators have evaluated the role of chemotherapy without irradiation in preventing local

recurrence after BCS. An Ontario study involving patients with node-positive disease

identified a subset of 121 premenopausal patients who had undergone BCS and for whom no

breast irradiation was given but who had received a 12- or 36-week course of systemic

adjuvant chemotherapy. The rate of local recurrence was lower after the longer, 36-week

systemic treatment with the combination of cyclophosphamide, methotrexate and 5-

fluorouracil (CMF) plus vincristine and prednisone (CMFVP) than after 12 weeks of

treatment (23% v. 39%, p = 0.02). However, these recurrence rates were not sufficiently

reduced to justify replacement of breast irradiation with chemotherapy alone.17 In the trial

from the Scottish Cancer Trials Breast Group, 585 women who underwent BCS were

randomly assigned to receive or not receive radiation therapy. All received systemic therapy,

with either tamoxifen or intravenously administered CMF according to the estrogen receptor

status of the tumour. The local relapse rate among those receiving radiation therapy was 5.8%

compared with 24.5% among those who did not receive radiation therapy (level I evidence).13

6

Recently, several trials have investigated the role of tamoxifen alone after lumpectomy in

women considered to be at lower risk of local recurrence. In the NSABP B-21 trial, 1009

women with node-negative breast cancer and tumours 1 cm in diameter or smaller treated by

lumpectomy were randomly assigned to receive tamoxifen alone, breast irradiation alone or

tamoxifen plus breast irradiation. About 80% of the women were 50 years of age or older.

The average follow-up was 7.2 years. The rate of local breast recurrence at 8 years was 16.5%

with tamoxifen alone, 9.3% with radiation alone and 2.8% with tamoxifen plus irradiation (p

< 0.01 for all comparisons) (level I evidence).18 Overall survival was not significantly

different between the treatment arms.

In a Canadian trial, 769 women over 50 years of age (median age 68 years) with tumours less

than 5 cm in diameter and pathologically or clinically node-negative were randomly assigned

after lumpectomy to receive tamoxifen (20 mg/d for 5 years) or tamoxifen plus breast

irradiation.19 The median follow-up was 3.4 years. The rate of local recurrence at 4 years was

6% in the tamoxifen group and 0.3% in the tamoxifen plus irradiation group (p = 0.009). In

an Intergroup trial, 647 women 70 years of age or over with estrogen-receptor (ER) positive

tumours less than 2 cm in diameter and pathologically or clinically node-negative were

randomly assigned after lumpectomy to receive tamoxifen or tamoxifen plus breast

irradiation. The median follow-up was 2.3 years. The annual rate of locoregional recurrence

was 0.9% with tamoxifen alone and 0% with tamoxifen plus irradiation (p > 0.05).20

In summary, the results of the NSABP trial indicate that the risk of local breast cancer recurrence

in patients who receive tamoxifen without irradiation is high. The results of the Canadian and

Intergroup trials suggest that older women with small ER-positive tumours who receive

tamoxifen without breast irradiation may have a lower risk of recurrence, but follow-up is still

too early to recommend that radiation therapy not be given.

Contraindications to breast irradiation

• Contraindications to breast irradiation include pregnancy, previous breast

irradiation (including mantle irradiation for Hodgkin's disease) and inability tolie flat or to abduct the arm. Scleroderma and systemic lupus erythematosus arerelative contraindications.

For some patients, physical disabilities, such as inability to lie flat or adequately abduct the

arm, can make irradiation difficult or impossible. Also, previous high-dose irradiation to the

thorax precludes further radiation therapy. Increased rates of acute and late radiation effects

have been reported among patients with pre-existing collagen vascular disease, including

scleroderma and systemic lupus erythematosus.21,22 Although a study involving 122 patients

using a matched cohort design suggested no statistical difference in acute or late

complications between patients with collagen vascular disease and normal controls, the

power to detect a difference was low and a proportion of the cases in the collagen vascular

disease group in fact had rheumatoid arthritis, which is not considered a contraindication to

irradiation.23 Thus, based on present evidence, scleroderma and systemic lupus erythematosus

should be considered relative contraindications to radiation therapy. When these conditions

are present, women should be made aware that the risk of local recurrence is increased

without radiation therapy and that this outcome can be avoided by mastectomy.

7

Radiation techniques

• A number of different fractionation schedules for breast irradiation have been used.

Although the most common fractionation schedule in Canada to date has been 50Gy in 25 fractions, recent data from a Canadian trial demonstrate that 42.5 Gy in 16fractions is as good as this more traditional schedule.

In planning therapy, the 2 main considerations are controlling local recurrence and obtaining

a satisfactory cosmetic outcome. In the 6 randomized trials of breast irradiation versus no

irradiation after lumpectomy already discussed, 3-14 only 2 used the same radiation

fractionation schedule5,14 (Table 1). Fractionation schedules used in these trials ranged from

40 Gy in 16 fractions to 54 Gy in 27 fractions administered to the whole breast with or

without boost irradiation to the primary site. Each fraction of radiation was delivered daily

Monday to Friday. In patients with comparable stages of breast cancer and similar lengths of

follow-up, the rates of local recurrence were similar (level III evidence). Prospective and

retrospective cohort studies have also reported acceptable rates of local control and cosmesis

with similar fractionation schedules.24-28

A commonly used fractionation schedule in Canada has been 50 Gy in 25 fractions to the whole

breast without boost irradiation when the margins of surgical excision are clear of disease (the

same schedule used in the NSABP studies). 29 The Ontario Clinical Oncology Group (OCOG)

recently reported the results of a Canadian randomized trial in which the more traditional, longer

course (50 Gy in 25 fractions administered over 35 days) was compared with a shorter course

(42.5 Gy in 16 fractions over 22 days) in women with node-negative breast cancer following

lumpectomy.30 Ten cancer centres in Ontario and Quebec and 1234 women participated in the

trial. The median follow-up was 5.8 years. No difference was detected in the rates of local

recurrence or cosmetic outcome at 5 years (level I evidence). The rates of local breast recurrence

were 3.2% in the long treatment arm and 2.8% in the short treatment arm (absolute difference

0.4%, 95% confidence interval -1.5% to 2.4%). The trial was limited to patients whose breast

was less than 25 cm in width at the midpoint of the radiation field. It is unclear whether the

results of this study apply to women with larger breasts, who may be more prone to poor

cosmetic outcome when radiation techniques are not optimized. Although the trial was restricted

to patients with node-negative disease, the observed results are likely generalizable to patients

with node-positive disease.

• Irradiation to the whole breast rather than partial breast irradiation is

recommended.

In a trial comparing irradiation to the whole breast and partial breast irradiation, 708 patients

were randomly assigned after BCS to receive either whole or partial breast irradiation.24,31 At

a median follow-up of 8 years, local relapse rates were 13% in the whole breast irradiation

group and 25% in the partial breast irradiation group (p = 0.00008) (level I evidence).

8

• There is insufficient evidence to recommend breast irradiation with brachytherapy

implants or intraoperative radiation therapy. Further evaluation of these treatmentsin randomized trials is required.

Recently there have been a number of phase I and II studies demonstrating that partial breast

irradiation with brachytherapy implants may provide adequate local control with acceptable

cosmetic outcome in selected patients.32,33 Local intraoperative radiation therapy is also being

evaluated.34 Further data from randomized trials are necessary before making definitive

recommendations about the role of brachytherapy alone or intraoperative radiation therapy

following lumpectomy.

• Additional irradiation to the lumpectomy site (boost irradiation) reduces local

recurrence but can be associated with worse cosmesis compared with no boost. Aboost following breast irradiation may be considered in women at high risk oflocal recurrence.

The role of additional irradiation to the lumpectomy cavity, called boost irradiation, has been

evaluated in 3 randomized trials (Table 2). In the Lyon trial, 1024 patients with tumours 3 cm

in diameter or smaller and clear margins following lumpectomy were randomly assigned to

receive radiation therapy with 50 Gy in 20 fractions over 5 weeks to the whole breast plus a

boost to the primary site of 10 Gy in 4 fractions over 1 week or radiation therapy with 50 Gy

in 20 fractions over 5 weeks to the whole breast with no boost.35 The boost was delivered by

a direct field using 9 or 12 MeV electrons. Approximately 50% of the patients received

adjuvant chemotherapy or tamoxifen. The median follow-up was 3.3 years. The rate of local

recurrence at 5 years was 3.6% among patients who received the boost and 4.5% among those

who did not (p = 0.044) (level I evidence). More patients in the boost group than in the

control group had telangiectasia (12.4% v. 5.9%, p = 0.003). No difference in survival was

detected between the groups.

In the Nice trial, 664 patients with invasive breast cancer treated by lumpectomy were

randomly assigned to receive radiation therapy with 50 Gy in 5 weeks plus a boost of 10 Gy

in 1 week or radiation therapy with 50 Gy in 5 weeks alone.36 The boost was delivered by

electron beam or reduced cobalt tangents. At a median follow-up of 6.1 years, the rate of

local recurrence was 4.3% among patients who received the boost and 6.8% among those

who did not (p = 0.13) (level II evidence).

The European Organization for Research and Treatment of Cancer (EORTC) conducted a trial

involving 5318 patients with early breast cancer who had clear resection margins following

lumpectomy.37,38 Patients were randomly assigned to receive radiation therapy with 50 Gy in 25

fractions to the whole breast plus a boost to the primary site of 16 Gy in 8 fractions, using an

external beam (direct electrons, tangent photons) or brachytherapy, or radiation therapy with 50

Gy in 25 fractions to the whole breast alone. Approximately 80% of the patients had nodenegative

disease and 28% received adjuvant systemic therapy. The median follow-up was 5.1

years. The rate of local recurrence at 5 years was 4.3% among patients who received the boost

and 7.3% among those who did not (p < 0.001) (level I evidence). No difference was detected in

survival between the 2 groups. A good or excellent cosmetic outcome was produced in 71% of

the patients who received the boost, compared with 86% of those who did not (p < 0.001).

9

Patients less than 50 years old were at higher risk of local recurrence than were older women, and

in this group of patients the absolute benefit of a boost appeared greater.

The results of these studies indicate that boost irradiation to the primary site in patients with clear

resection margins reduces the risk of local recurrence. However, the absolute benefit is small,

and the use of a boost is associated with a poorer cosmetic outcome. Results of the EORTC study

suggest that the absolute benefit may be in the order of 4%-10% for women less than 50 years of

age. In the Canadian trial the rates of local breast recurrence were very low (3.2% in the long

treatment arm and 2.8% in the short treatment arm).30 These rates are lower than the rate in the

boost arm of the EORTC trial. Among women less than 50 years of age in the Canadian trial, the

rates of local breast recurrence were 3.6% in the short treatment arm and 7.2% in the long

treatment arm. For such women the potential benefit with boost irradiation would be of a

relatively small magnitude.

Controversy also exists regarding further management when the pathologist reports

microscopic involvement or close resection margins with invasive cancer or DCIS.39-42

Patients with positive margins following lumpectomy are at increased risk of local

recurrence, and re-excision or mastectomy should be considered, especially if there is more

than focal involvement (see guideline 3). Patients should be informed when margins are

involved, and if surgery is declined it is normal practice to recommend boost irradiation.

Similarly, patients with close resection margins (i.e., tumour approaches this margin by 1-2

mm) may be at increased risk of local recurrence, but data are conflicting. The effectiveness

of boost irradiation for positive or close resection margins remains unclear.

Oncologists may wish to consider the use of a boost (10-16 Gy in 4-8 fractions) in women at

increased risk of local recurrence following breast irradiation alone (e.g., those < 40 years of

age, or those with positive or close resection margins). Patients should be informed about the

absolute benefits and risks.

• Physicians should adhere to standard treatment regimens to minimize the adverse

effects of breast irradiation.

BCS followed by breast irradiation is associated with very few significant complications.30

The frequency and severity of complications and poor cosmetic results increase with the use

of unusual dosages or dosage schedules, or when regional node irradiation is used as well.43

Negative health effects of irradiation

• When choices are being made between different treatment options, patients must

be made aware of the acute and late complications that can result from radiationtherapy.Skin erythema and fatigue are common short-term side effects of radiation therapy.

The cause of fatigue is not known; it is maximal in the first few weeks to months after

radiation therapy. Skin erythema and fatigue usually resolve completely within 3 to 6 months.

Such symptoms and the inconvenience of radiation therapy can affect a patient's quality of

life.44 In the Canadian randomized trial that evaluated the role of breast irradiation after

10

lumpectomy,44 patients' quality of life was assessed at baseline and at 1 and 2 months

following randomization. Patients treated with radiation therapy had little change in quality

of life over the 2-month period, whereas those who did not receive radiation therapy had

steady improvement in quality of life. The difference between groups was statistically

significant (p = 0.0001).

Mild and moderate long-term effects of irradiation are relatively rare.

During the first 2 years after surgery and radiation therapy, patients may experience skin

irritation and intermittent pain in the breast.27,45-47 These symptoms are usually self-limiting

and seldom severe.44 In the Canadian trial that compared radiation therapy and no radiation

therapy after lumpectomy,10,44 both skin irritation and breast pain were more frequent at 3 and

6 months after treatment in the patients who received radiation therapy than in the control

patients. The proportion of patients with symptoms steadily decreased over time, so that at 2

years skin irritation was reported by only 7% of the patients and breast pain by 15%

regardless of whether the patients received radiation therapy.44

Other effects that may be experienced up to 5 years after BCS followed by breast irradiation

include mild breast erythema (6%), mild breast edema (3%), moderate or severe breast

induration (2%), and mild (13%) or moderate to severe (1%) telangiectasia over the breast

area.27

Lasting cosmetic sequelae of irradiation may become visible after the first year and progressfor several years.

These sequelae do not appear to worsen significantly after approximately 3 years.27,47,48

Evaluation of cosmetic outcome has primarily been based on physician evaluation in case

series.47-51 A satisfactory result is reported in 80%-95% of cases.27,45,50,52,53 In the Canadian

trial, patients were asked to report any trouble or upset regarding the appearance of the breast

on a regular basis.44 Breast irradiation did not increase the proportion of patients at 2 years

who were troubled by the appearance of the treated breast (4.8% of patients in the irradiated

and non-irradiated groups, p = 0.62).

In a study from British Columbia, cosmetic results were reported to be satisfactory by 89% of

physicians and 96% of patients.27 Localized fat necrosis was reported in 1%-8% of patients,

particularly in high-boost areas. This side effect is self-limiting and harmless but may be

confused with local recurrence.27,53

Severe long-term adverse effects of irradiation are rare.

Older case series in which women received breast and nodal irradiation reported the

following rare complications (< 1%): pneumonitis, pericarditis, rib fracture, brachial

plexopathy and arm edema.51,52,54 However, many of these complications were associated

with techniques involving regional nodal irradiation and large total doses and fraction sizes

that are no longer in use. With current irradiation techniques following lumpectomy, such

complications will probably occur extremely rarely, if at all.

Investigators have evaluated the risk of death from myocardial infarction following breast

11

irradiation after lumpectomy. Rutqvist and associates reported no increase in the risk of

myocardial infarction related to left-sided versus right-sided cancers in a population-based

cohort of 684 Swedish women who were treated with breast irradiation.55 The median followup

was 9 years. Similarly, in an institutional-based study, Nixon and associates reported no

increase in cardiac deaths related to laterality among 745 patients followed for a minimum of

12 years following breast irradiation.56 Paszat and colleagues reported the results of a

population-based study involving 3006 patients treated in Ontario between 1982 and 1987.57

They found that at 10 years' follow-up, 2% of the women who had received radiation therapy

for left-sided cancer had a fatal myocardial infarction, compared with 1% of those who had

been treated for right-sided cancer (p = 0.02). Recently, Vallis and colleagues reported on the

risk of fatal and nonfatal myocardial infarction in a similar cohort of patients treated at the

Princess Margaret Hospital between 1982 and 1989.58 A total of 2128 patients were

evaluated. Care was taken to review the diagnosis of myocardial infarction according to

prespecified diagnostic criteria. At a median follow-up of 10.2 years, no excess in cardiac

disease was identified among patients who had received radiation therapy for left-sided

cancer compared with those who had been treated for right-sided cancer. Despite the overlap

in the populations, the difference in the results of the 2 latter studies may reflect a different

methodology used to identify myocardial events and potentially different radiation therapy

practices at different centres; for example, regional radiation therapy was used in only about

8.5% of cases at the Princess Margaret Hospital during the study period.

In the recent meta-analysis by the EBCTCG, 20-year results from 40 randomized trials were

evaluated (level I evidence).15 Although a reduction in the rate of death from breast cancer

was observed, an increase in cardiovascular deaths was demonstrated. The majority of trials

contained in the analysis were trials of locoregional radiation therapy after mastectomy. In the

trials of breast irradiation, a significant increase in cardiovascular deaths was not observed.

In a retrospective analysis involving 825 women taking part in randomized trials in Milan,

Valagussa and associates reported a modest increase in the occurrence of cardiac failure

among patients who received anthracycline-containing regimens and breast irradiation (4/501

patients receiving adriamycin v. 3/114 receiving adriamycin plus irradiation of the left

breast).59 In a study by Shapiro and colleagues, an increased risk of cardiac disease was

demonstrated only among patients who received a moderate to large portion of irradiation to

the heart and 450 mg/m2 of doxorubicin.60

In summary, it is unlikely that irradiation to the left breast is associated with an increased risk

of death from cardiac causes. Nonetheless, it would be prudent to exercise caution in treating

women with left-sided breast cancers when radiation therapy may involve the anterior aspect

of the heart.

The risk of malignant disease resulting from breast irradiation after BCS is very low.

It has been suggested that breast irradiation may cause an increase in 3 types of malignant

disease: breast cancer, sarcoma and leukemia.

Breast cancer: In a case-control study involving women under 45 years of age, a marginally

significant elevation in risk of contralateral breast cancer was found following breast

12

irradiation after mastectomy.61 However, for most patients, other relevant risk factors such as

family history and histologic subtype were not reported. Other studies have failed to show a

connection between irradiation and contralateral breast cancer (level III evidence).62-64 Thus,

at present there is no convincing evidence to support any such association. Nevertheless,

techniques should be used that minimize exposure of the opposite breast, especially in

younger women (level IV evidence).

Sarcoma: Most reports regarding the association of sarcoma with radiation therapy have

involved orthovoltage therapy and regional as well as local breast irradiation.51 Current

evidence suggests that the risk of radiation-associated soft-tissue sarcomas is approximately 1

in 1000 patients per decade of follow-up.53,65

Leukemia: In a case-control study involving 82 700 women with breast cancer diagnosed

between 1973 and 1985, there appeared to be a significant increase in risk of acute

nonlymphocytic leukemia after regional radiation therapy, which increased with increasing

dosage. However, after the exclusion of patients treated with alkylating agents, the relative

risk of leukemia attributable to radiation therapy alone was not statistically significant.66

Recently, the NASBP reported results from trials in which patients received adjuvant

chemotherapy with doxorubicin and cyclophosphamide. Six trials involving 8533 patients

contributed over 50 000 patient-years of follow-up. Thirty-nine cases of acute myeloid

leukemia or myelodysplastic syndrome were observed. The incidence of leukemia or

myelodysplastic syndrome was increased among patients who received more intensive

chemotherapy (relative risk 6.72, p = 0.0001) or breast irradiation (relative risk 2.45, p =

0.007).67 This is the first report of an increased risk of leukemia with breast irradiation among

women who received chemotherapy.

If the risk of leukemia is increased because of breast irradiation, the magnitude of the

increase in absolute terms is very small. Clearly, this cannot be considered a contraindication

to postoperative radiation therapy.

Time interval between surgery and radiation therapy

• Breast irradiation should be started as soon as possible after surgery and not later

than 12 weeks after, except for patients in whom radiation therapy is preceded bychemotherapy. However, the optimal interval between BCS and the start ofirradiation has not been defined.

The timing of radiation therapy has been studied in a cohort study involving 436 patients.

Patients who began radiation therapy more than 7 weeks after BCS appeared to be at greater

risk of recurrence than patients receiving treatment earlier (14% v. 5%).68 However, the

interval between radiation therapy and surgery was not significant when other relevant factors

were considered in a multivariate analysis (level V evidence). Likewise, in a study involving

653 patients with node-negative breast cancer who received a dose of 60 Gy or greater to the

primary tumour site, when risk factors were controlled, there was no difference in the

recurrence rates associated with intervals ranging from 4 to 8 weeks between surgery and

radiation therapy (level V evidence).69

13

There remain a number of conflicting reports regarding the risk of recurrence following delay

in radiation therapy after lumpectomy. Slotman and associates reviewed 508 cases of patients

with stage I or II breast cancer treated with breast irradiation after lumpectomy (level V

evidence).70 At a median follow-up of 5.7 years, the rate of local recurrence was 1.7% among

patients who started radiation within 7 weeks after surgery and 5.6% among those with a

longer interval (p < 0.05). In a Cox proportional-hazard analysis, the interval between surgery

and radiation remained predictive of local recurrence (p = 0.003). Froud and associates

reviewed 1962 cases of women in British Columbia at low risk for recurrence who did not

receive chemotherapy (level V evidence).71 At a median follow-up of 5.9 years, they found

no difference in ipsilateral breast recurrence for intervals between surgery and radiation

therapy of 0-20 weeks. However, the risk of distant recurrence was significantly higher with

intervals of more than 12 weeks between surgery and the start of radiation therapy.

In the absence of better evidence, any recommendation must rest on general principles. Thus,

undue delay should be avoided. The Royal College of Radiologists of the United Kingdom

set a maximum of 4 weeks as a target, but in a survey reported in 1995, only 55% of patients

in the UK received radiation therapy within this interval.72 However, the consensus of the

contributors to this guideline is that 4 to 8 weeks may be a reasonable delay, but a delay of

more than 12 weeks should be avoided except when chemotherapy is administered first.

Sequencing of chemotherapy and radiation therapy

• The optimal sequencing of chemotherapy and breast irradiation is not clearly

defined for patients who are also candidates for chemotherapy. Most centresfavour the administration of chemotherapy before radiation therapy. Selectedchemotherapy regimens are sometimes used concurrently with radiation therapy.There is no evidence that concurrent treatment results in better outcome, andthere is an increased chance of toxic effects, especially with anthracyclinecontainingregimens.

The issue of sequencing arises when breast irradiation and adjuvant chemotherapy are being

planned. There are several options, including the delivery of all chemotherapy before

radiation therapy; the delivery of radiation therapy before chemotherapy (both of these

options are termed "sequential regimens"); the simultaneous institution of chemotherapy and

radiation therapy (concurrent regimens); and the initiation of radiation therapy in the midst of

a chemotherapy program (sandwich regimens). The choice may influence survival, diseasefree

survival and cosmetic outcome.

The 2001 update of a study by Recht and associates73 reported the results for 244 patients

treated with lumpectomy who were randomly assigned to receive radiation therapy before or

after chemotherapy.74 The median follow-up was 11.3 years. There was no significant

difference in time to any failure, time to distant metastases or time to death between the 2

groups. The recurrence rates by site of first failure were also similar between the 2 groups

(local recurrence 15% v. 13%, respectively; distant recurrence 26% v. 32%, respectively)

(level II evidence). This study was relatively underpowered to detect differences in failure

patterns. The timing of radiation therapy has been considered in other studies, with

inconsistent results (level V evidence).75-79

14

In several trials designed to evaluate adjuvant chemotherapy regimens after BCS, radiation

therapy was delayed until chemotherapy was completed, without any apparent increase in

local recurrence (level I evidence).80-83

Apart from questions of survival and local recurrence, several case series have shown that

when chemotherapy and radiation therapy are given concurrently, the potential for increased

acute and late adverse effects of radiation therapy, including a worse cosmetic outcome, is

increased.83-85 This is especially so when anthracycline-based regimens are used (level III

evidence).84

Clinical trials

• Patients should be offered the opportunity to participate in clinical trials

whenever possible.

As frequently noted above, the knowledge base for many of the interventions involved in the

treatment of breast cancer is often extremely weak or does not exist. These particular areas of

uncertainty, where recommendations must, at present, be based on level III, IV or V evidence,

can be eliminated only by well-designed, randomized, controlled trials. Improvement in the

care of future patients with breast cancer thus depends on the participation of sufficient

numbers of patients in such trials. Physicians treating patients with breast cancer should,

therefore, be aware of currently available trials, and patients should be given the chance to

participate.

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30. Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized

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40. Fourquet A, C

mdb,

I think I am understanding that your position is, at least in part, due to your unique situation.  My teenage daughter died from rhabdomyosarcoma, a very rare, very aggressive cancer of the skeletal muscle.  Leiomyosarcoma is similar but of the smooth muscles.

In my experience, I can assure others that bc and these cancers are as different as any other two diseases.  I don't want to sound like I am trivializing bc as I have stage IIIb IDC and my mom had DCIS.  However, I suspect that having had gone through a sarcoma, bc seems to be the lesser of two evils.  Although I went through aggressive chemo, rads and many surgeries, it was nothing compared to the hell that my daughter went through.  Perspective is everything.

To Worried Hubby,

Thank you for posting, that research. Although, it was really long, and I'll admit, I only had time, to skim it.

 But the phrase that came out, for me, which I've seen before, "No difference in life expectancy, with or without, the raditaion. 

I'm not stupid. I don't want, to die. But when reading that, in all of the studies, why do, the radiation?

Like I said. I'll NEVER do it. With a low-grade, breast cancer.

mdb

Worried Husband, et.al.,

I've been following this discussion with interest. 

But, just now responding.  That is a huge radiation bill.  It caused me to check my own statements from last year.  My actual radiation treatments, not boosts or set-ups, were about $600 a piece, and the weekly visit with the rad onc was billed at $225.

The radiation is extremely individualized.  The physics department of each hospital is involved in calculating the exact prescription of each persons radiation tx.  The rad onc is only one part of the team involved.  Keep in mind, these professionals not only treat breast cancer, but brain cancer, bone cancer, prostate cancer, liver cancer, etc. 

Re stats:  The difference in statistics for recurrence of cancer between mastectomy and lumpectomy/radiation would depend on many variables ... type of cancer (IDC vs. ILC vs. DCIS), stage, grade, margins, patient age, ER/PR HR type.  Also, mortality rate is considered death ... period.  You can still be alive, but under tx for a Stage IV cancer or a recurrence.  So mastectomy vs. lumpectomy/radiation mortality rate is a little deceiving. 

Statistics have an enormous difference in meaning depending on the type and stage of cancer you have.  A 5% difference in mortality or recurrence rate, when deciding tx options and risks, may not be as important to someone with a Stage I dx, as to someone with a Stage III dx.  The same goes for the statistics when calculating the risk/benefit of taking an antihormonal medication.  Which has been my personal issue ... and an appropriate discussion for another thread.

Husband ... wish your wife all the best.

Thanks all for such a lively discussion,

Bren

Survival Improved by Radiation After Breast Cancer Surgery

Key Words

Breast cancer, radiation therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

Combined data from 78 randomized clinical trials show that radiation therapy after either breast-conserving surgery (BCS) or mastectomy in women with early breast cancer significantly reduces both five-year recurrence and 15-year mortality rates. This is the first research to show that postsurgical radiation therapy in this group of patients helps them to live longer in addition to lowering their risk of local recurrence.

Source

The Lancet, Dec. 17, 2005 (see the journal abstract).
(Lancet. 2005 Dec 17;366(9503):2087-106)

Background

In women with early-stage breast cancer treated with surgery alone (breast-conserving surgery or mastectomy), microscopic residual disease may not be eliminated and can eventually cause life-threatening metastatic recurrence. Radiation therapy after surgery has been widely recommended for women at high risk of recurrence, based on the results of clinical trials showing that such treatment cuts the rate of local recurrence (a return of cancer in the remaining breast tissue, scar, chest wall, or nearby lymph nodes).

However, the same trials, taken individually, have failed to show whether these women actually lived longer thanks to the additional radiation therapy.

For that reason, even with widespread support, these recommendations are not always heeded. When detected early enough, local recurrence can often be treated with additional surgery alone, so some physicians and patients still elect to avoid radiation therapy and its associated side effects.

The Study

Combined data (called a meta-analysis) from 42,000 women - collected from 78 randomized trials begun between 1958 and 1991 - was performed by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG). The availability of extensive 15-year survival data allowed the investigators to reliably quantify the relationship between successful local control and long-term survivorship.

The individual trials compared varying types of local control:

• radiation therapy after breast-conserving surgery (BCS) vs. no radiation therapy after BCS
• postmastectomy radiation therapy vs. no postmastectomy radiation therapy
• more extensive surgery vs. less extensive surgery
• more extensive surgery versus less extensive surgery, with radiation therapy after both
• more extensive surgery vs. less extensive surgery, with radiation therapy only after less extensive surgery

The EBCTCG reviewed the trial results for how long it took breast cancer to recur; whether recurrence was local or distant; mortality (due to breast cancer or otherwise); and the incidence of second primary cancers before breast cancer recurrence.

Results

Radiation therapy after breast-conserving surgery was responsible for a highly statistically significant reduction in local recurrence. Combined, the data showed a 19 percent absolute reduction of the risk of recurrence five years after treatment. Although none of the trials showed a significant reduction in 15-year mortality when analyzed on their own, the meta-analysis revealed a highly significant absolute reduction of 5.4 percent.

For women with cancer that had spread to the lymph nodes (node-positive) and who underwent a full mastectomy, postoperative radiation therapy provided a similar reduction in recurrence and mortality: a 17 percent absolute reduction of the risk of recurrence five years after treatment and a 5.4 percent reduction in 15-year mortality.

When subgroups were analyzed, the investigators found that the higher the risk of recurrence, the greater the potential benefit of post-surgery radiation therapy. The investigators concluded that for any group of early breast cancer patients, a local treatment difference that reduces the five-year local recurrence risk by 20 percent would reduce the 15-year breast cancer mortality by 5.2 percent.

In other words, says Jeff Abrams, M.D., of the National Cancer Institute's Cancer Therapy Evaluation Program, "for every four local recurrences that are avoided by the addition of radiation therapy, about one breast cancer death could be avoided over the next 15 years."

Limitations

The one drawback of radiation therapy noted by the EBCTCG meta-analysis was an increase in the incidence of secondary cancers (new cancers unrelated to the original breast cancer) and in mortality from heart disease and lung cancer. However, the investigators emphasize that modern radiation therapy technology now minimizes the radiation doses to the heart, lungs, and other breast, compared to the doses given at the time these trials were conducted.

Comments

"These long awaited results from the EBCTCG overview analysis demonstrate an important effect for adjuvant radiation therapy in the treatment of primary breast cancer," says Abrams, noting that the survival benefit is apparent both in women who undergo breast-conserving surgery and those with cancer in their lymph nodes who undergo a mastectomy.

The authors place their results in the context of combination therapy, and state that "the moderate differences in 15-year breast cancer mortality produced by better local control can be combined with the moderate differences produced by chemotherapy and hormonal therapy...yielding in total quite substantial effects on 15-year breast cancer mortality."

I had radiation last year.  I had stage 1 no nodes involved -estrogen -, so I wasn't a candidate for tamoxifen.  The oncologist also suggested chemo which I denied.  I thought it was over-kill, since it increased my chances of not returning by a few percent.  I was wondering why rads was needed.I wish I knew about this website last year.  

Rose