ATM Variants of Unknown Significance and Radiation

[Mandelin Rain]

As MyRisks are being ordered with greater frequency on breast cancer patients, I've seen a couple young ladies with ATM VUSs and don't really know what to do about radiation recommendations. The clinical information states that they are "probably benign" but I'm unconvinced when I'm looking at a 20-something year old with stage III breast cancer.

Obviously bad cancer, that I would normally reflexively recommend post mastectomy radiation, but is that placing excess risk of second malignancy or other severe complication? There is certainly data demonstrating such in known deleterious mutations with HRs ranging 2-5. But these VUSs... who knows?

I feel it's best to treat the cancer she's got appropriately and worry less about the potential stuff down the road. But it's never satisfying seeing a second malignancy.

Any thoughts?

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[Gfunk6]

Even for patients with clinically active connective tissue disease, there is not an absolute recommendation against treatment. The pause really kicks in when someone has systemic scleroderma or SLE with either uncontrolled symptoms or on "significant" anti-inflammatory medications. Generally, I think it would be safe to ignore ATM variants without clinical manifestations.

These silly tests really screw us - if you don't treat and the patient recurs you are screwed; if you do treat and the patient has a bad reaction you are screwed.

 

[medgator]

Weigh the remote risks of that vs the very real and more common risk of locoregional recurrence with the pt. We know from the danish and ebctcg meta-anlaysis that local recurrences kill patients and impact OS numbers long term, especially in a younger patient who is going to have an increasing risk of recurrence without appropriate treatment the longer they live

 

[Mandelin Rain]

Weigh the remote risks of that vs the very real and more common risk of locoregional recurrence with the pt. We know from the danish and ebctcg meta-anlaysis that local recurrences kill patients and impact OS numbers long term, especially in a younger patient who is going to have an increasing risk of recurrence without appropriate treatment the longer they live

Definitely agree in this case. I guess I was more curious in general. Say a 45 yo with DCIS and some VUS in ATM or p53. Anyone changing anything they do radiation-wise?

 

[BobbyHeenan]

As an aside, I recently treated a patient (~65 years old) with no prior history of collagen vascular disease, etc. Never had joint issues or skin thickening in the past, etc...

First 1-3 months after treatment she's fine and doing well... then at 6 month follow up she has full blown active scleroderma. Thickened bilateral skin of hands and forearms...and her treated breast is rock hard with woody fibrosis (imaging showed no underlying masses, just skin thickening). Craziest thing I've ever seen. Luckily it's not painful and her PCP has her in with rheumatology soon, but active scleroderma with whole breast XRT doesn't go well.

I'm hoping that with anti-inflammatories the breast gets less fibrotic, but probably not. There's a reason why they say active scleroderma is a contraindication. I've treated a good bit of lupus or sjogren's patients (even ones requiring ongoing anti-inflammatory treatments) and they've done fine...but this fibrosis was unforgettable.

 

[Mandelin Rain]

As an aside, I recently treated a patient (~65 years old) with no prior history of collagen vascular disease, etc. Never had joint issues or skin thickening in the past, etc...

First 1-3 months after treatment she's fine and doing well... then at 6 month follow up she has full blown active scleroderma. Thickened bilateral skin of hands and forearms...and her treated breast is rock hard with woody fibrosis (imaging showed no underlying masses, just skin thickening). Craziest thing I've ever seen. Luckily it's not painful and her PCP has her in with rheumatology soon, but active scleroderma with whole breast XRT doesn't go well.

I'm hoping that with anti-inflammatories the breast gets less fibrotic, but probably not. There's a reason why they say active scleroderma is a contraindication. I've treated a good bit of lupus or sjogren's patients (even ones requiring ongoing anti-inflammatory treatments) and they've done fine...but this fibrosis was unforgettable.

I've seen one case of scleroderma diagnosed because of her late XRT reaction. You'd have thought a blow torch was taken to her chest. Unforgettable is correct. Try Trental and Vit E?

 

[medgator]

I've seen one case of scleroderma diagnosed because of her late XRT reaction. You'd have thought a blow torch was taken to her chest. Unforgettable is correct. Try Trental and Vit E?

Yup. Will take years to see an effect probably

 

[BobbyHeenan]

I've seen one case of scleroderma diagnosed because of her late XRT reaction. You'd have thought a blow torch was taken to her chest. Unforgettable is correct. Try Trental and Vit E?

Yeah, I put her on that. She tolerates it fine, but I doubt it'll do much. She says it's not painful but I can't imagine how it's not painful; sweet, tough lady. I felt/feel awful. I went back through her chart carefully to make sure I didn't miss anything and quizzed her about rheumatological stuff and she never had anything even remotely resembling scleroderma (undiagnosed) in the past. She now has classic findings for it.

 

[Cancerdancer]

I currently have a ES-SCLC pt with active scleroderma, all the stigmata, including facial skin tightness/trisums. 4 small asymptomatic brain mets. Lots of systemic burden, asymptomatic brain mets, so started systemic first. 50ish. Was planning WBRT between cycles. Would anyone instead do SRS? Was thinking the soft tissue in a WBRT field should be too much of a problem but these anecdotes get me nervous...

 

[medgator]

I currently have a ES-SCLC pt with active scleroderma, all the stigmata, including facial skin tightness/trisums. 4 small asymptomatic brain mets. Lots of systemic burden, asymptomatic brain mets, so started systemic first. 50ish. Was planning WBRT between cycles. Would anyone instead do SRS? Was thinking the soft tissue in a WBRT field should be too much of a problem but these anecdotes get me nervous...

I just gave low-dose WBRT to 31 y/o F with primary CNS lymphoma and scleroderma, used similar logic to yours, she just finished, crossing my fingers, the dose was in the 20s though. I would do WBRT, personally. I think the areas to worry about are H&N, breast, esophagus, lung, abd/pelvic organs etc.

 

[BobbyHeenan]

I currently have a ES-SCLC pt with active scleroderma, all the stigmata, including facial skin tightness/trisums. 4 small asymptomatic brain mets. Lots of systemic burden, asymptomatic brain mets, so started systemic first. 50ish. Was planning WBRT between cycles. Would anyone instead do SRS? Was thinking the soft tissue in a WBRT field should be too much of a problem but these anecdotes get me nervous...

Even after seeing what I saw (severe breast fibrosis), I'd still do WBRT on this patient.