negative nodes ending up with Mets - numbers?

http://www.lifeabc.org/risk_recurrence_more.html

Risk of Recurrence in Early Breast Cancer

Clinical management of patients with early breast cancer is determined on an individual basis, taking into account many factors, including the risk of cancer recurrence. The clinical management of breast cancer is directly linked to pathological assessment of the cancer so accurate pathological interpretation of the breast cancer specimen is vital.

Common factors have been identified for predicting risk of recurrence in patients with breast cancer. They include:

Lymph Node Involvement

• Whether the tumor has spread to the lymph nodes at the time of diagnosis (node-positive) and, importantly, the number of lymph nodes in which cancer has been found.

Tumor Size

• Factor in determining the stage of breast cancer

Histologic Grade

• Grade is a calculation based on how abnormal the cancer cells look under a microscope and how fast they are growing. There are 3 features when determining a cancer's grade: (1) the rate of cell division, (2) percentage of cancer composed of tubular structures, and (3) change in cell size and uniformity. If a tumor has been determined to be Grade 3 then there is a higher risk of recurrence than if the tumor was determined to be Grade 1.

HER2/neu (a growth-promoting protein) Status

• Gene that helps the growth of cells, how they, divide, and repair themselves. Positive or negative HER2/neu is important in the control of abnormal or defective cells that could become cancerous and might have implications for treatment. 15

Lymphatic Vessel Invasion (LVI)

• When pathologists look directly at the cancer under a microscope they determine whether cancer cells are found in the lymphatic vessels within the cancer itself.

Hormone Receptor Status:

• This status reflects whether the cancer is estrogen receptor positive (ER+) or not

(ER-) or progesterone receptor positive (PgR+) or not (PgR-). This status may have some prognostic information and, at this time, is used to plan treatment.

Health care professionals use these prognostic factors to help determine recommendations for appropriate adjuvant therapy and whether additional treatment should be considered after adjuvant therapy has been completed. 11,16,17

In 2005, the St. Gallen International Consensus Panel, a panel of experts in the field of early breast cancer, revisited risk categories for patients with ER/PgR-positive early breast cancer and determined that to qualify as "minimal-risk" [also called low-risk], all of the following criteria need to apply: cancer has not spread to the lymph nodes; tumor is <2 cm in greatest dimension; nuclei are small, with little increase or variation in size compared with breast epithelial cell nuclei, regular outlines, uniformity of nuclear chromatin; no cancer cells have invaded the blood or lymphatic vessels and cancer does not use the HER2neu pathway to grow

Better understanding of actual ongoing risk in all patients, including "low-risk" patient populations, is critical for optimizing treatment decisions. In this paper we will discuss some of the latest data that have emerged surrounding the risk women with early breast cancer face in terms of their disease returning.

Clinical Research

Node-negative status at diagnosis has commonly been associated with a favorable patient outcome. However, long-term risk of recurrence and death are not well understood. Many current studies support the notion that there is a risk of recurrence for women with early breast cancer regardless of nodal status, estrogen receptor status, age, chemotherapy regimen, time on tamoxifen or time from initial diagnosis. 14

Ongoing risk

Many people have the misconception that after successful initial treatment, patients with early breast cancer who remain disease free for five years or more (according to existing tests) are unlikely to experience a recurrence of their cancer. However, recurrences can occur after five years.

In a meta-analysis (from seven different studies) of more than 3,500 patients who had received some type of post-surgical adjuvant therapy for breast cancer, risk of cancer recurrence was greatest during the first two years following surgery. After this period, the research showed a steady decrease in the risk of recurrence until year five when the risk of recurrence declined slowly and averaged 4.3% per year.18 But a substantial proportion of breast cancer recurrences seen in this study occurred more than five years after surgery, between years six and 12, even in patients who typically would be considered at low risk for recurrence because their cancer had not spread to the lymph nodes at the time of diagnosis (node-negative).18 What this research indicates is that through at least 12 years of follow-up, the risk of breast cancer recurrence remains appreciable and even some patients considered low risk have some risk of the cancer coming back.

Another meta-analysis, this one of nearly 37,000 women with early breast cancer, conducted by the Early Breast Cancer Trialists' Collaborative Group, found:

• Through the first 10 years after diagnosis, the cumulative incidence of recurrence and breast cancer-related deaths continued to increase, with a substantial portion of recurrences and breast-cancer related deaths occurring beyond five years after diagnosis.
• The recurrence rate among patients who did not receive adjuvant hormonal therapy was nearly 50% in node-positive patients and 32.4% in node-negative patients throughout the first 10 years after diagnosis. 9

These data showed that some years of adjuvant tamoxifen treatment substantially improved the 10-year survival of women with estrogen receptor-positive (ER+) tumors and of women whose tumors are of unknown ER status, even in women who had node-negative disease. 9

Another analysis of recurrence among ER+ patients found that use of tamoxifen therapy significantly improved patient outcomes in a population considered to be at minimal risk prior to this trial. However, even with adjuvant therapy, more than 20% of node-negative patients had their disease recur within 15 years after diagnosis. 11

Confirming these findings, a recent study showed that even for small tumors in the lowest risk category, the 10-year risk of breast cancer recurrence was as high as 12% in the absence of adjuvant therapy. Additionally in the absence of adjuvant therapy, even in the lowest risk category, the 10-year risk of breast cancer-related death is high, at 7%. 14

Another study showed that more than half of all breast cancer recurrences and two-thirds of all breast cancer deaths occur after completion of five years of standard tamoxifen therapy. 19

A study evaluating the risk of breast cancer recurrence following adjuvant therapy in 2,420 patients with early breast cancer showed that there was a substantial and continuing risk of recurrence long after completion of five years of standard adjuvant treatment. 20 Additionally, after the first five years, there were similar proportional rates of recurrence for node-negative and node-positive breast cancer patients. 20 Data from the National Surgical Adjuvant Breast and Bowel Project B-14 trial showed, however, that continued use of tamoxifen after five years was associated with an increase in serious adverse events, but no further efficacy benefits. 11

Many studies conducted in breast cancer reveal that most adjuvant therapies are essential tools in the fight against breast cancer as they decrease the risk of recurrence by at least one-third. But the ongoing risk of recurrence in patients with very small tumors and no nodal involvement points to the need to continue research into even greater improvements in ways to determine accurately a woman's risk of recurrence in order to evaluate the best treatment options available. Furthermore, it is essential that health care professionals communicate these findings with their patients while discussing treatment options.

As part of the treatment process, the risks and benefits of possible treatment options are necessarily discussed. In terms of the adjuvant therapy most commonly used, tamoxifen, the American Cancer Society indicated that tamoxifen can increase the risk of developing cancer of the lining of the uterus (endometrial cancer). This cancer is usually diagnosed at a very early stage and is generally curable by surgery. Tamoxifen can also increase the risk of uterine sarcoma, a rare cancer of the connective tissue of the uterus. Blood clots are another serious side effect of tamoxifen. Other side effects may include weight gain (although recent studies have not found this), hot flashes, vaginal discharge and mood swings. 21

http://www.breastcancer.org/treatment/chemotherapy/new_research/20050629.jsp

I prefer to look at this when I feel "unsure"..lol.

Thanks lexislove.  We must have been posting at the same time.

Jilly - to understand your own personal risk of recurrence/mets, did you have an Onocotype DX test done? My score was 22 - which put me at a 14% risk of recurrence without chemo. With chemo and Herceptin, my recurrence was cut in half to 7%..........much better odds, but still HIGHER than my original risk was calculated for getting breast cancer in the first place. Thus, I don't place much confidence in risk assessment...........it's all a crap shoot as far as I'm concerned, sigh.......but still I do my best as to rolling my dice in this game of chance and have been a "good girl" listening to my onc's advice.

Part of the problem, from what I've read lately, is that we are undertreated as node negative. It is surprising researches how quickly we progress to mets...

I have only had a bilat mast in December of last year with no hormonal treatment, no rads and no chemo, and have stamped my foot to see an onc. I am having my FIRST appointment on July 31st! Can you believe it??????

I will be pretty annoyed to say the least, if I develop mets quickly. I was at first relieved to not be recommended by my surgeon for more treatment, but now I realize how foolish I was to let my surgeon dictate my cancer treatment!

barbe1958 - Is what you've been reading pertain to our sisters in Canada?  I live in New York and at first everyone (the surgeon, radiation onc, etc.) was saying surgery, radiation & hormone therapy.  Once I saw the medical oncologist, based on the pathology, she was considering chemo - lymphovascular involvement.  I did not have chemo because of the Oncotype test, but despite having radiation & Tamox I'm a little freaked out that I could develop mets despite being node negative.  I don't blame you for being annoyed!  I hope when you finally get in there you get the excellent care you deserve.

Sue

Let's make it clear that for ER+ women who stay on treatment, these recurrence numbers are significantly improved. The quotes I gave are for recurrence risks off hormonal treatment.

The Oncotype DX too (or Mammoprint) has added greatly in helping define a low risk group who appear to do well just with hormonal therapy. These numbers are not to dismiss this personalized test in any way and ones oncologist's recommendations which follow from it. Low grade, slow growing ER+ bc with negative nodes (or some may say with scant + in one or so node) treated with aromatase inhibitors (pretty much now advised first in the US) or tamoxifen do very well. My post is to encourage frank discussion with your oncologists about 5 years and after from diagnosis and the issues regarding recurrence vs lowering the risk with continuence of hormonal therapy. Lastly, more clinical trials will soon yield results regarding the 5 -10 year and 10 year plus ER+ clinical situation (MA-17 for one).

Surely though, don't second guess your original treatment. Many stage 1 ER+ women are now treated with hormonals after surgery and/or rads, not chemotherapy. Stage II women are more complicated as we know, and most still get chemotherapy unless again their oncologists feels their node is minimal disease

Its very important to focus this discussion so not to scare ourselves and invoke a sense of doom or dread. This is never our goal here. Perhaps too our goal is to warn the Oncology Community that many outside of oncology do not know the facts as spelled out here, and restraint in pushing us off to possibly uninformed health care providers is warranted.

My best to you all,

Tender

I would strongly recommend having the Oncotype testing done!  My tumor was 2.6 cm, which puts me at stage IIa, grade 1, ER+/PR+, HER-2 -, 0/14 nodes.  My Oncotype score was 13 which showed I had an 8% chance of distant metastasis in the next 10 years if I chose Tamoxifen alone.  If I chose chemo the chance dropped to only 7%.  My oncologist and I decided since the tumor was well differentiated and that chemo would only drop the recurrence rate by 1% the risks of chemo did not outweigh the benefit.  I did opt for bilateral mx which were done on 6/18 so I don't have to worry about any more biopsies. 

Again the oncotype testing can help deciding whether or not chemo is right for you.

I hope,and I will push my onc, to continue with some form of anti estrogen pill after I finish my 5 years of Tamoxifen. I strongly feel continuing with these meds are beneficial, even though nothing"big" has come out regarding this.

Terri, you have the exact same picture in your avatar as someone else on the boards! I thought you were her...hehehehhee

We are really talking about two completely different topics on this thread. 

The original question asked about women with negative nodes going on to develop mets.  I haven't seen anyone address that question.  I haven't seen any studies of the percentage of women who go on to develop a distant metastasis without a new primary tumor.  They may be out there, I just haven't seen them.

Most of the posts here have dealt with recurrence percentages.  Whether or not your nodes are negative has no bearing on the likelihood of you developing a new primary cancer.  The chances of any woman in the general population developing breast cancer in her lifetime is currently 1 in 8, and rapidly heading toward 1 in 7.  The frequently cited 20% of node negative women whose only treatment is surgery will go on to have a recurrence works out to 1 in 5.  

Whatever combination of genetics and lifetstyle and exposure to toxins etc. combined to cause the cancer to develop in the first place still happened to us.  It makes sense that we are at higher risk of developing a new primary cancer in our breasts, or of having cells that are left behind from the original tumor flaring up again than women in the general population.  That is very different from developing metastatic cancer in a different site which is what the original question was about. 

There are no guarantees in health care, and if your surgeon missed even a couple of cells of breast tissue, a new primary can start in them.  I had the bilateral too, and I've found a couple of lumps since then. The good news is that you notice the lump very quickly since it is just under the skin, not buried in large lumpy breasts.  The radiologist informed me that the first couldn't be cancer since there is no breast tissue left.  The surgeon did a biopsy because there could be some breast tissue left that was hiding.  The other good news is that the biopsies have been b9. 

Barbe- glad your oncologist is working with you on your questions/findings. I know it's a stressful time and hope you feel our support.

Helena-the ATAC trial analyzed joint tamoxifen and arimidex use, and results showed less effect taken together, i.e., better results taken separately. I believe the tamoxifen lowered the effectiveness of the arimidex.

Shelly- I don't know the stats you are seeking. Perhaps the HER2 board ladies would be able to help you with your question on recurrence in HER+ state. You might try posting over there.

Jilly- I'll stand on 20 to 30% of ER+ node negative women in years past untreated except for surgery with additional chemo/hormonals who progressed with time, as this is based on the early NSABP statistics from which Love most likely gleaned her number. The key to that statistic is further untreated.

In this day and age of SLN (sentinal lymph node) biopsy, it is clearer why those early statistics in breast cancer treatment resulted. Bessie from this site posted a link which I copy below, which delves into retrospective studies of the lymph nodes in women called lymph node negative and what pathologists subsequently found when re-studied in detail (ie, single cells, micromets etc). The paper is dense but gives you an idea why the original numbers of 20 to 30% were quoted, and why newer techniques of fingerprint IHC and much more now result in a node being called positive when years earlier it would have been lumped in the negative. The call of a positive node of course then also brings further treatment to discussion in the last decade plus. SLN really did revolutionize breast cancer diagnosis and treatment.

Lastly, one more point regarding the Oncotype Dx. A result that is in the "low" range supports a recurrence score of about 7%. One recent research group points out that a discrepancy between the low score and the individual's Ki-67 result (a result which measures cell turnover) may account for those 7% and urge oncologists to consider and discuss the Ki-67 score with patients if it is higher than expected for an overall "low" score. Perhaps these patients, if ER+, would want to know this so they can further analyze the merits of chemotherapy etc in addition to hormonal treatment. 

As we can see from this thread, breast cancer knowledge is a work in process.

Tender

Link: http://www.annalssurgicaloncology.org/cgi/content/full/11/3_suppl/227S#TBL1

Patmom writes:The frequently cited 20% of node negative women whose only treatment is surgery will go on to have a recurrence works out to 1 in 5. 

Patmom, where did you get that figure? More info is needed.

You need to ask, what kind of surgery? Local recurrence? Distant recurrence? Also, it is important to ask, what the survival numbers are, not the recurence numbers. Check for absolute risk, not relative risk.

Women frequently get local recurrence at the incision site because of poor surgical technique (spilling cells due to roughness) or the surgeon didn't get it all. The recurrence often has nothing to do with the aggressiveness of the cancer. That's why so many of our grandmothers survived with mastectomy only.