Chief of Research
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Your questions are excellent and your concerns if not alarming quite justified and prudent. So I'll try to untangle the issues below and provide for you a way to think about these matters b based on the best balance of the evidence to date.
LCIS First the facts, briefly: for stage I–II breast cancer such as yours, local recurrence occurs in approximately 10%–20% of patients treated with BCS (breast-conserving surgery, aka lumpectomy), which is significantly reduced by postoperative radiotherapy, but the reduction is primarily a reduction of - not ipsilateral contralateral - breast tumor recurrence.
As to LCIS, its biological significance as a "
risk indicator" versus a " breast cancer precursor" has been a matter of considerable debate. Note that the risk indicator nature of LCIS is not in dispute - in fact, it is widely accepted that LCIS confers a modest increased risk of development of invasive carcinoma of about 1 to 2% per year, with an 8-year risk of about 4.4 - 4.7%, 10-year risk of between 7% and 8%, a lifetime risk of 30 to 40%, and a relative risk of breast cancer of 8 to 10-fold.
Now, as to the balance of the latest evidence, it suggests:
That LCIS is both a risk indicator and a precursor of invasive breast cancer; what this means is that LCIS should be considered a predisposing determinant of risk for subsequent invasive disease in either breast, but as a non-obligate / non-inevitable precursor the development of subsequent invasive carcinoma is not assured, although its risk is elevated, and the invasive carcinoma, should it develop, is not necessarily assured to be of lobular histology. non-obligate Nonetheless, as a preneoplastic state from which progression may not be inevitable, LCIS is in general a reversible condition of low biologic potential and typically slow progression to invasive cancer if any. Local recurrence risk (LRR) varies somewhat with tumor size, with tumors > 3cm sustaining higher risk, and with young age (< 50) being an independent significant factor. Risk reduction with unilateral mastectomy is only modest, and it is for this reason that PBM (prophylactic bilateral mastectomy) needs to be considered an option for selected patients, based on the cumulative weight of all risk factors. The landmark NSABP P-1 Study established that progression to invasive disease seems to be significantly inhibited by the use of tamoxifen. A Warning Now. although the standard of care with LCIS is currently close follow-up together with chemoprevention via tamoxifen, the recommendation of your PCP to deploy the other SERM, raloxifene (Evista) instead of tamoxifen is in error and wholly against the evidence, and would lead to a false and dangerous illusion of preventive value: as decisively shown in the recent STAR trial, one of the largest breast cancer prevention clinical trials ever conducted, raloxifene (Evista) is of no significant benefit of risk reduction in LCIS; while tamoxifen was been shown to reduce by half the incidence of both LCIS and DCIS, raloxifene (Evista) did not have any appreciable effect on these diagnoses. And this result confirms data reported earlier in 2004 from the large CORE study of raloxifene (Evista). And, unlike tamoxifen which is chemopreventive in both premenopausal and postmenopausal women, raloxifene (Evista) is sanctioned, and of value, only in the postmenopausal setting. Multifocality Multifocal disease describes cases in which two or more discrete tumors can be detected clinically, radiographically, or pathologically in the same breast; the term multicentric is used to describe multiple independent primary tumors in one breast, in contrast to multifocal which describes multiple tumor nodules derived from a single primary tumor and that occur close (in the same quadrant as the primary tumor) to the primary lesions. Multifocality is well-established as a significant risk factor for local recurrence, largely because it is thought to represent intramammary spread, but this is in part dependent on whether it is a case of multifocal LCIS versus multifocal DCIS: currently, the significance of multifocal LCIS differs from multifocal DCIS, as there is considerable doubt as to the malignant potential of the cells in LCIS, but nonetheless the multifocal LCIS incurs non-obligate elevated risk of local recurrence, which may not develop inevitably, and which may be countered by effective preventive intervention, either chemoprevention and/or prophylactic surgery. Breast Density Dense breasts - breast that are highly fibroglandular and so contain proportionately less fatty tissue - is one of the most consistently established factors for elevated breast cancer and recurrence. The stock explanation which you quoted from the mammography report, is that "underlying breast tissue is dense, limiting mammographic sensitivity" suggesting that the elevated risk is largely consequent to compromised detection, but in fact the risk is known to be wholly independent of this: carcinoma in breast fatty tissue is exceedingly rare, as it commonly embeds in the connective tissues (lobes and ducts) and collagen structures of the breast - even if it were perfectly detectable without error, the risk remains since dense breasts simply contain far more "at risk" structures.
The good news is that breast density can be appreciably reduced if not wholly eradicated by various effective interventions: robust physical exercise, minimal near-null consumption of alcohol, and a low-(saturated) fat diet as lifestyle interventions, and calcium (1500mg/daily in three divided doses as the citrate or phosphate salt, not carbonate) and
HD-D3, that is, high-dose Vitamin D3 (3000 IUs/daily) as nutritional interventions, all can appreciable reduce breast density, and therefore, associated risk. Surveillance Given breast density, and the elated risk of LCIS and multifocality, mammography should be supplemented by MRI, which is demonstrably superior in detecting multifocal lesions, and in detecting any potential malignancy in dense breasts. I typically advise an "interleaved" scheduling - both yearly, but one (either) six months after the other rather than at the same time, assuring no more than six months before another surveillance is scheduled. In addition CBE (clinical breast examination) is of value if not rushed and in the hands of an expert.
I am unaware of any compelling evidence that surveillance more frequently than at the six month point is of material benefit, but should you want to "simulate" it, ultrasound scheduled at at least one 3 month point may provides some modest extra assurance. (As to calcifications, being declared benign, the only concern would be a rare malignant foci hiding among the benign calcifications, but a multimodal surveillance program of mammography, MRI and intermittent ultrasound is the best means of addressing any such small eventuality).
Another Warning Now be aware that an in-press study that is due to appear in JCO within the next several weeks by the radiation oncologist Lawrence Solin at the University of Pennsylvania is likely to make a considerable splash and be massively misinterpreted by the popular and even medical literature - indeed, the accompanying editorial by Monica Morrow at Fox-Chase is entitled "Magnetic Resonance Imaging in the Breast Cancer Patient: Curb Your Enthusiasm", but I reviewed the study pre-publication, and there are some significant limitations: (1) nonrandomized, retrospective analysis of a cohort of patients from a single institution, and (2) with an 8-year rate of local recurrence of about 4% for patients not doing a breast MRI study, this baseline rate is sufficiently low that demonstrating a statistical improvement would be exceedingly difficult and unlikely in a retrospective cohort study like this, and in any event would require a substantially larger sample size than the tiny 756 patients evaluated. In addition, more critically compromising is (3) the limitation of the treated patients to largely ones at low risk for local recurrence, with predominantly negative margins, predominantly small tumors, and a high rate of adjuvant systemic therapy for those patients with invasive carcinomas.
Somehow it does not seem to have occurred to the study authors nor to the normally sensible Monica Morrow that using a study population of predominantly low-risk patients to evaluate the benefit of breast MRI, a technology of known benefit and applicability to high-risk patients,
, is against common sense. Given these considerations, had I been on the reviewing panel I would have strongly advised against publication of both the original study and the accompanying editorial. Regrettably, the field will have to shortly deal with the long-term fallout of this study's misinterpretation and highly circumscribed relevance (if any). by definition Final Thoughts The elevation of risk by the combined factors of LCIS, multifocality, and breast density (and possibly age, although I am unaware of yours in this case) motivates (1) both robust surveillance as I outlined above, (2) possibly surgical prophylaxis in the form of BPM (prophylactic bilateral mastectomy) and/or (3) some component of oncoprevention. As to one form of prevention, namely chemoprevention, here, assuming tamoxifen has proved intolerable, and knowing that raloxifene (Evista) is of zero benefit as I indicated above, your options - assuming you are not already postmenopausal - are ovarian ablation, either surgical as oophorectomy, or medical, as ovarian suppression via LHRH/GnRH analogs like goserelin (Zoladex) or leuprolide (Lupron) to induce a true menopausal state which then makes you a candidate for aromatase inhibitor chemoprevention (and of course if already postmenopausal, then AI therapy is motivated).
And of course, you are quite right, a frank discussion of the prognostic significance and impact of LCIS, multifocality, and breast density (and young age and/or premenopausal status if relevant) should have been systematically presented to you, and all these preventive and risk reductive options weighed and explored, so that surveillance alone not be construed as your only, or best, defensive posture.
A Bombshell Before I Close Finally, I should just note that there is emerging evidence, especially some forthcoming seminal findings from Kirstin Jensen at Stanford, that the assay bar for HER2-positivity should be lowered to a ratio of 1.5, far below the current recommended cut point of 2.2, a position I have been a strong and long-term advocate of (and which our ever-insightful moderator Gina hit upon early on, and we harmonized), and although we need more critical mass of supporting data to be absolutely dispositive - which I believe is indeed arriving from various quarters - this may entail the option of anti-HER2 therapy for you, given as you state borderline HER2 status, and I would even now take that as tantamount to sufficient HER2-positivity to treat you as endocrine and HER2 responsive. Constantine Kaniklidis Breast Cancer Watch firstname.lastname@example.org