metastatic breast Ca that responded very well to CT.....

[Kroll2013]

Dear Colleagues,

What would you do in this case?

57 years old female with no comorbidities, that presented with a metastatic breast carcinoma.
Locally, the tumor was very locally advanced ulcerating into the skin and invading the pectorals with high burden of disease in the axilla.
Pet CT showed: positive nodes in the mediastinum, hilarious regions and many lung nodules.
she is ER/PR+, Her2 negative, IDC.
she received upfront chemotherapy with significant response:
- significant regression of the primary tumor and axillary nodes; persistant lesion still taking the skin and abutting the pectoralis.
-significant response of the thoracic nodes but still residual activity present
- complete resolution of all the lung nodules.

she was referred for palliative radiation to the breast and axilla to maximise local control.

question: is surgery ( radical mastectomy + ALND) followed by radiation instead of radiation alone an option for this patient ?

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[Palex80]

I would not give RT but rather "consolidate" with an aromatase inhibitor (+ a CDK-4/6-inhibitor).

Unless she has symptoms from the breast tumor or the nodes, there is no clear benefit by delivering RT right now in my opinion.

I would have suggested treatment if she had presented with distant lymph-node only disease or a solitary bone met, but this lady had multiple lung nodules. There is a great chance that she will respond to endocrine treatment and you never know where the disease is going to progress next.

I would also avoid surgery by all means. The morbidity of a mastectomy + ALND in this situation (controlled disease, palliative scenario) is too great and the benefit in doubt.

 

[scarbrtj]

The question of mastectomy (EDIT: and hasn't it usually been "toilet" mastectomy instead of full-monty mastectomy?) in stage IV breast cancer rears its head every few years; on the whole, correct me if I'm wrong, it's been a wash. Re: Palex's suggestion to palliate sans RT, it depends on the nature of the local disease. If it's the size of a nickel, I guess hold the RT. If she looks like Michelangelo's model from The Night, however, treat now. If her disease makes it hard to keep her bra clean, treat. Or, especially, if the disease is bothering other people in the room even when the patient is dressed... XRT it.

 

[Palex80]

Re: Palex's suggestion to palliate sans RT, it depends on the nature of the local disease. If it's the size of a nickel, I guess hold the RT. If she looks like Michelangelo's model from The Night, however, treat now. If her disease makes it hard to keep her bra clean, treat. Or, especially, if the disease is bothering other people in the room even when the patient is dressed... XRT it.

True, true, if the disease is bothering her, you have an indication for RT. However: Response rates to endocrine therapy + palbo are likely to be quite high too.
I presume the reason the patient received first line chemotherapy instead of endocrine therapy was widespread lung metastases?
Otherwise one could have simply given her first line endocrine treatment instead of the chemotherapy?

 

[Krukenberg]

There are randomized trials in this setting that aren’t talked about much in rad onc

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00135-7/fulltext

Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01 - PubMed

In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV...

www.ncbi.nlm.nih.gov

Both randomized to surgery in stage IV breast cancer. Primary outcome (OS) was negative in both but in the Turkish study, with longer follow up the surgery arm appeared to have better survival. Unplanned subgroup analyses suggested young, limited mets benefitted more. I would expect radiation-only treatment would achieve inferior survival outcomes so I don’t think these support radiation for local control.

 

[scarbrtj]

I presume the reason the patient received first line chemotherapy instead of endocrine therapy was widespread lung metastases?
... I would also avoid surgery by all means.

Yeah in my neck of the woods almost all of these patients get anti-E and something like Ibrance (which I suppose is standard of care now instead of just anti-E alone) upfront as opposed to chemo upfront. I don't know that I'd say avoid any surgery "by all means," but an out and out radical mastectomy here would be wacky. And a traditional ALND on top of that (or as part of that, whatever) would be super wacky.

 

[evilbooyaa]

We do it (surgical resection +/- adjuvant RT I mean) at my institution for the sake of 'being aggressive' but I really don't like it and wouldn't. I also would not radiate at this time. She has diffusely metastatic disease and despite her good response I'm not a fan of treating off protocol. You have some data I suppose to back it up given the MF07 trial linked above but I'm not overtly enthusiastic for it and think it needs to be offered to very well selected patients. I'd actually be more inclined if she had a good resopnse everywhere but the breast and axilla.

I would not radiate without surgery. If everyone has made the decision to be aggressive and the patient gets a surgery, IMO it's not my place to contradict everyone and withhold PMRT for classical PMRT indications.

I will say in regards to the posted case - MF07 did not allow for T4 disease at presentation to be enrolled (depends on level of skin involvement initially, given it's still involved after chemo?)

 

[scarbrtj]

I also would not radiate at this time... I'd actually be more inclined if she had a good resopnse everywhere but the breast and axilla.

This (a good response everywhere, less so in the breast primary) is actually what I envisioned after reading Kroll's vignette...
"she received upfront chemotherapy with significant response:
- significant regression of the primary tumor and axillary nodes; persistant lesion still taking the skin and abutting the pectoralis.
-significant response of the thoracic nodes but still residual activity present
- complete resolution of all the lung nodules."

 

[mavrik13]

Of the available treatment options, surgery would have more evidence supporting it than radiation. That being said, in a younger patient (in all likelihood, someone who is 57 with metastatic breast cancer will die of their cancer), I'd support being aggressive.

With a very aggressive local tumour, I like the idea of mastectomy, SLNB if she has had complete clinical response, ALND if not and adjuvant RT. Yes it is likely overkill, but I think that is easier to tolerate when she is feeling well and on antiestrogen versus when she has progressed after 3rd line chemotherapy/hormonal therapy and is symptomatic. While she won't die of a local recurrence, it is likely easier to treat now when the volume is disease is small than when she has a terrible local recurrence.

If the patient/surgeon is not interested in an aggressive approach with surgery, I would only consolidate with RT if the patient is symptomatic now.

 

[Bequerel]

This is a judgement call. Easier to be aggressive when bone only mets as we know prognosis is better. In our group we are aggressive with younger patients (30’s and 40’s) and less so with older patients (60’s and 70’s). This one seems to fall right in the middle and you could argue both ways.

On a side note...I’ve been thinking more about my follow-up imaging patterns. I was trained, and NCCN seems to recommend, to use limited imaging with follow-up. Now that we are starting to learn that we can improve outcomes with aggressive treatment of oligometastatic disease, it makes sense to look for such potential disease? Has anyone changed their follow-up imaging schedule accordingly?

 

[evilbooyaa]

This (a good response everywhere, less so in the breast primary) is actually what I envisioned after reading Kroll's vignette...
"she received upfront chemotherapy with significant response:
- significant regression of the primary tumor and axillary nodes; persistant lesion still taking the skin and abutting the pectoralis.
-significant response of the thoracic nodes but still residual activity present
- complete resolution of all the lung nodules."

More inclined for surgery + RT is what I meant. I would almost never radiate these off-protocol without the patient undergoing surgery.

For me the 'ideal' scenario and the purpose behind that comment would've been 1) complete resolution of all lung nodules, 2) no residual activity in hilar/mediastinal LNs, and 3) persistent disease in breast/axilla (maybe a PR, maybe stable disease)

 

[evilbooyaa]

This is a judgement call. Easier to be aggressive when bone only mets as we know prognosis is better. In our group we are aggressive with younger patients (30’s and 40’s) and less so with older patients (60’s and 70’s). This one seems to fall right in the middle and you could argue both ways.

On a side note...I’ve been thinking more about my follow-up imaging patterns. I was trained, and NCCN seems to recommend, to use limited imaging with follow-up. Now that we are starting to learn that we can improve outcomes with aggressive treatment of oligometastatic disease, it makes sense to look for such potential disease? Has anyone changed their follow-up imaging schedule accordingly?

I mean I get SABR-COMET included breast patients, but I don't think it's going to make me get surveillance CT C/A/Ps on every stage III breast going forward, in the same way that I don't do CT C/A/P or indefinite PET/CT for all my stage III NSCLC patients. Low threshold to image something that hurts or is otherwise symptomatic, sure.

 

[medgator]

I mean I get SABR-COMET included breast patients, but I don't think it's going to make me get surveillance CT C/A/Ps on every stage III breast going forward, in the same way that I don't do CT C/A/P or indefinite PET/CT for all my stage III NSCLC patients. Low threshold to image something that hurts or is otherwise symptomatic, sure.

Agree. Guessing symptoms will help declare those patients with distant (often later) recurrences, with consideration for ablative therapy if they are oligometastatic

 

[scarbrtj]

More inclined for surgery + RT is what I meant. I would almost never radiate these off-protocol without the patient undergoing surgery.

For me the 'ideal' scenario and the purpose behind that comment would've been 1) complete resolution of all lung nodules, 2) no residual activity in hilar/mediastinal LNs, and 3) persistent disease in breast/axilla (maybe a PR, maybe stable disease)

Of the available treatment options, surgery would have more evidence supporting it than radiation... With a very aggressive local tumour, I like the idea of mastectomy, SLNB if she has had complete clinical response, ALND if not and adjuvant RT... If the patient/surgeon is not interested in an aggressive approach with surgery, I would only consolidate with RT if the patient is symptomatic now.

You guys would countenance de-pectoralizing (now that seems off-protocol in Stage IV disease) a lady with a history of metastatic lung nodules and local disease invading the chest wall muscles? 'Cause you're gonna have to here if surgery's your therapy. Countenance lymphedema-izing her? The ALND already is already the redheaded stepchild of therapeutic benefit in non-metastatic breast cancer and somehow it's going to change natural history in Stage IV with visceral mets?? What if you had metastatic disease and a normal arm, and later your doc gave you this plus metastatic disease due to a willingness for "aggression?" Of course none of us have personally examined the patient to see the present state of her local disease which undoubtedly would color and/or change our choices here.
(On another note: wish we'd ditch the "aggressive" talk. It's lost its meaning. I mean, there's "aggression" and then there's chemo, RT, surgery, CAR-T therapy, etc. And then there's unwise. Is an APR with bilateral inguinal LND instead of chemoRT for anal cancer a more aggressive treatment e.g.?)

 

[Palex80]

(On another note: wish we'd ditch the "aggressive" talk. It's lost its meaning. I mean, there's "aggression" and then there's chemo, RT, surgery, CAR-T therapy, etc. And then there's unwise. Is an APR with bilateral inguinal LND instead of chemoRT for anal cancer a more aggressive treatment e.g.?)

It's not more "aggressive" per sé. It's a different treatment with definitive loss of the organ. An organ which does have a function, which itself is quite important for almost all patients.

But I do understand what you want to say and I endorse it.

Brain surgery, 60 Gy of radiation therapy, half a year of temozolomide and tumor treating fields are also "aggressive treatment" for glioblastoma. Yet at the end, every (or almost every) patient dies within 5 years and half of them are dead at 2 years. Still we deliver this kind of treatment on a daily basis for young and fit patients.

 

[mavrik13]

You guys would countenance de-pectoralizing (now that seems off-protocol in Stage IV disease) a lady with a history of metastatic lung nodules and local disease invading the chest wall muscles? 'Cause you're gonna have to here if surgery's your therapy. Countenance lymphedema-izing her? The ALND already is already the redheaded stepchild of therapeutic benefit in non-metastatic breast cancer and somehow it's going to change natural history in Stage IV with visceral mets?? What if you had metastatic disease and a normal arm, and later your doc gave you this plus metastatic disease due to a willingness for "aggression?" Of course none of us have personally examined the patient to see the present state of her local disease which undoubtedly would color and/or change our choices here.
(On another note: wish we'd ditch the "aggressive" talk. It's lost its meaning. I mean, there's "aggression" and then there's chemo, RT, surgery, CAR-T therapy, etc. And then there's unwise. Is an APR with bilateral inguinal LND instead of chemoRT for anal cancer a more aggressive treatment e.g.?)

I don't disagree with your main points (though perhaps a little over sensationalized), but if she has had a good response elsewhere and it is possible to render someone NED with surgery/RT, that may be worthwhile to consider in a young(ish) patient.

While it is comparing apples to oranges, the Gomez trial shows that aggressive consolidative therapy in NSCLC with limited metastases after upfront chemo has improves OS (phase 2 trial not withstanding).

Uncontrolled local recurrences in the breast suck, and I like the idea of treating when intervention will cause the least amount of morbidity (i.e. if PR, can the surgeon remove a section of the pec major vs entire muscle?). Either way - your point is taken and it is tough to know what the right thing to do is