Sorry took so long...my cable was out yesterday.
On my surgery rotation the attendings and residents constantly espoused the idea that "for all that we've accomplished with chemo, surgery, and screening mammograms...we have not improved mortality in breast CA."
To put it bluntly, your attendings and residents are wrong. We HAVE improved mortality over all in breast cancer. Using the National Cancer Institute's SEER database (Surveillance, Epidemiology and End Results) the survival rates over the last twenty five years have improved for all age groups in patients with locoregional disease, and the age-adjusted breast cancer mortality rate for all white women has decreased. The decreases are most steady since the early 90s. Every other important study looking at the issue of mortality agrees with the NCI data; we have decreased mortality in all age groups, across all races, for locoregional disease.
The issue becomes more clouded when you look at race; while the death rate has declined somewhat for African Americans, it has not done so nearly as much as it has for whites. Some of this is due to the later stage at which AAs are often diagnosed; despite the widespread use of screening mammography, AAs are still disproportionately diagnosed later (by way of comparison, 20 years ago only 35% of white women were diagnosed in Stage 1; now it approaches 60% almost all of which is likely to be due to the increased use of mammography and awareness). We also have not been as successful in decreasing mortality rates for patients with advanced disease; while inroads have been made, the vast majority of decreases in overall mortality are because of earlier diagnoses. Unfortunately, some patients have tumor biologies which are less favorable under current treatment plans and patients diagnosed with Stage 4 disease are still likely to die of their disease.
But when reading the textbooks, it appears that the 5yr prognosis is improving especially when detected earlier.
That is correct, although for African American women, the 5 year survival rates are lower than for white women - across the board: local disease, locoregional and metastatic breast cancer. Prognosis and survival dramatically increase with earlier stages of diagnoses.
Also, hasn't the use of SERMs increased survival stage for stage in ER/PR+ cancer? Likewise for aromatase inhibitors? And HER2-neu?
The increase in survival rates, particularly for women with locoregional disease reflects not only earlier diagnosis with screening mammography but also improvements in systemic adjuvant therapy via the use of multidrug combinations and better targeted agents. Results from the Early Breast Trialists Group note that multidrug chemotherapy (which I know you weren't talking about above, but figured I'd mention it) significantly reduces recurrence and mortality in node negative and positive patients regardless of age, stage or receptor status. It is important to note that the best evidence for the use of SERMS and/or AIs is not only to reduce mortality from breast cancer but also for risk reduciton - they reduce recurrence, increase time to recurrence and incidence of contralateral breast cancer. So they increase disease free survival rate by reducing the risk of recurrence by about 45% and the risk of death by 25% (mostly Tamoxifen data).
Herceptin, being used in a different population of patients, works best when used with chemotherapy. A number of small trials have shown a complete pathological response using herceptin as neoadjuvant treatment in 20-35% of patients. Much better numbers than using paclitaxel and FEC (which isn't widely used anymore).
Also, it is believed that OCPs do not appear to increase the risk of breast cancer. The WHI, on the other hand, showed that combined estrogen and progesterone increased the risk of breast cancer. Is the carcinogenic effect of E+P strictly a post menopausal phenomenon?
Despite early fears that OCPs increased the risk of breast cancer, the confounding factors that women who delayed childbirth are more likely to get breast cancer and women who have regular medical care are more likely to have breast cancer diagnosed (at least earlier), confused the issue. It does not appear that OCPs increase breast cancer, as you note.
The follow-up for women who partipated in the WHI study of hormone replacement is expected to continue until the end of 2007. While the study did show 8 more women in the estrogen-prog group developed invasive breast cancer than the placebo group, this was not significant and there was no observed increase in mortality in that group. There are some other problems with the WHI study - the women were, on average, 10 years older than the average menopausal woman - and a major one: the study was only 5 years in length which given the average time from initial growth to detectable tumor is 5 years...so these women were likely to have had their breast cancers when they enrolled in the study, regardless of which arm they were in; the drop out rate and the rate at which women started and stopped the meds were higher than predicated pre-enrollment. There's just too much wrong with the WHI data to form a definitive conclusion about the role of HRT in breast cancer. So I remain unconvinced that HRT increases the rate of breast cancer or that it has any effect on mortality. Just the same, I would advise any women with an ER/PR + tumor on HRT to stop the hormones.
What would be your approach to the following:
56 yo woman presents to LMD for clinical breast exam. No breast mass is found, but 2-3 axillary nodes are palpable.
- Would a mammogram be the "next best step in diagnosis?"
Yes. You must always have the basics before you embark on a treatment journey. Any woman with a suspcious mass (axillary or not) needs appropriate diagnostic imaging - in this case a bilateral diagnostic mammogram to start.
Obviously we are gonna have to harvest some lymph nodes, so say they came back positive for cancer...
- You have to assume she has systemic disease and needs chemo, correct? Will she need radiation?
I would probably FNA the nodes in the office if they are fairly shallow and reachable at the end of my needle, while awaiting the mammo and operating room time. Ax dissection is the standard of care for axillary nodes which are positive on FNA for breast mets and/or palpable. Of course there are cases of axillary lymphadenopathy being a CUPs but we will assume in your case that they are related to a breast cancer (the tricky question comes when you can't find a mass on mammo or MRI but you have positive nodes which appear to come from breast primary.)
A node positive patient requires adjuvant therapy with a combination chemotherapeutic regime. Most radiation oncologists would radiate patients with more than 4 positive nodes in the axilla (found on Ax Dissection) or fixed, matted nodes (N2 disease). (Obviously I am leaving out of the discussion post-operative radiation of the breast for local control).
So to answer your question, if she has positive nodes, she by definition has metastatic disease and cannot be cured of her disease. But she doesn't have to die of her disease and you must treat her as you see fit...with the data we have above, a young-ish patient with no other evidence of disease, so I would venture that all medical oncologists would be offering her systemic treatment.
- Next we have to figure out ER/PR, HER2-neu status to base our chemo?
Yes. The medical oncologist will not design a treatment protocol without tissue (ie, "no meat, no treat"). So I must provide them with enough tissue (usually via core biopsy, partial mastectomy or axillary dissection in this case to run receptor status on.
-Would we need a CXR for occult mets? CT of head, chest, abdomen, and pelvis? Bone scan only if symptomatic?
The standard, at least at our facility, is to order a CT of the chest abdomen and pelvis and total body bone scan. Brain mets are rarely occult so CT head without symptoms is low yield. We will have our CXR from pre-op testing from the axillary clearance. Some places add a whole body PET instead of bone scan and others may include bilateral breast MRI - a good idea if you cannot find a primary on mammo.
Of note, you may be interested to know that there is no data to suggest that routine post-treatment follow-up with markers or the above imaging tests change mortality. So, we do not routinely order regular ct scans or bone scans unless the patient is symptomatic. Patients on a SERM do get regular gyn exams (although the Gyns tend to go overboard and order regular TV ultrasounds and then biopsy when they see endometrial thickening...which is almost never endometrial CA) and bone density every couple of years. Patients on Doxorubicin get frequent MUGA scans every few months while on treatment, or when symptomatic.
This has been a confusing topic for me throughout the year and you appear to know your $hit so your input on this would be greatly appreciated.
You are not the only one. The topic changes rapidly and even attendings can get confused (I had one of my former attendings this year and a former co-resident both call me for "mini lectures" on breast right before their board recerts and initial board cert exams. Its hard to keep up to date). Hope this helps.
