Associate Professor Shane White | Breast Oncologist

sorry I haven’t posted for a while , New Years resolution-post more. I did tweet from SABCS if someone wants to follow my twitter feed at conferences. If I can see I have some interested followers it will motivate me to tweet more when I am away.

It was an interesting conference, and also was the first time it snowed in San Antonio for 28 years.

The medical highlights included more data supporting the use of CK4/6 inhibitors in advanced ER+ breast cancer, this time Monaleesa 7 (I was an investigator in this study) showing the benefit of ribociclib in premenopausal women with advanced breast cancer (ABC) , combined with goserelin and letrozole. This adds to a number of studies in post -menopausal women receiving any of the three inhibitors (ribociclib, abemaciclib and palbociclib). Ribociclib is now available for post-menopausal women with ABC through an access program. Pre-menopausal women would need a BSO (ovary removal) to gain access. There will be a study (PATINA) opening soon for patients with ER+ Her2+ ABC .

There was a meta-analysis (collected data from  many  studies) supporting the use of dose-dense chemotherapy as adjuvant therapy even in ER+ early breast cancer. previously such approaches at least in my practice were confined to triple negative early breast cancer.

There was some surprising randomised data supporting the use of acupuncture in the management of joint symptoms of patients receiving aromatase inhibitors (letrozole, anastrozole, exemestane).

There was lots of new science particularly focussing on immunotherapy(IO)  in breast cancer. only a subgroup of patients seem to benefit from IOs and we need to understand who can benefit from single agent PD1 inhibitors (checkpoint inhibitors) and who might derive benefit  from IO doublets or combinations with chemotherapy. My colleague Sherene Loi (Peter Mac) presented some interesting data on IO added to trastuzumab in patients with Her2+ve ABC previously treated with trastuzumab showing activity in a group of patients.

I am heading to the European meeting in March and may have more for you then.Cheers Shane

Hi all. 

It has been a while since last comments. San Antonio was a bust with me recovering from flu. Anyway, one of the best recent study outcomes was the POEMS study (http://www.nejm.org/doi/full/10.1056/NEJMoa1413204). This randomised study demonstrated conclusively that the hormonal implant goserelin can protect the ovarian function and therefore fertility during chemotherapy. This has huge ramifications for women receiving chemotherapy who still want to bear children or those wanting to avoid an early menopause. It is not government funded and will cost about between 700-1800$ depending on the length of the chemotherapy course.

It generates a temporary  menopause or hibernation of the ovaries if you prefer. Side effects may include hot flushes, mood disturbance and loss of libido.

This was a combination of 2  trials (SOFT/TEXT) for a total of  4690 premenopausal  pts with hormone drive early breast ca (ER+)

All were treated  with ovarian suppression (injections or ovarian surgery /radiation)  for 5 yrs and either tamoxifen or exemestane. Exemestane is an aromatase inhibitor  (AI)(like anastrozole and letrozole) which is superior to tamoxifen in the ppost menopausal setting. Thus, the SOFT/TEXT study aimed to emulate these results in premenopausal patients.

Overall 5yr DFS (prim endpt) was 91.1% for exe vs 87.3% tam. So there was a 4% improvement in freedom from breast cancer recurrence (helping an extra 1/25 patients). Some criticisms or concerns would include the lack of long  term followup and assessment of implications for bone  thinning (osteoporosis) and cardiovascular disease. The AIs can be challenging with higher rates of joint aches, mood disturbance and libido issues.

My sense is that this may suit the right premenopausal patient with higher risk disease who wants to maximise theie therapeutic gain and has maybe through chemotherapy not found the hormonal disruption troubling in the leadup to this discussion and consideration. A quirk of the PBS is that exemestane can only be used after prior TAM for 2-3 years but I don’ t regard its action as  having a therapeutic advantage over the other AIs which are PBS listed ‘up front’. http://www.nejm.org/doi/full/10.1056/NEJMoa1404037

At EBCC , the ZOOM data was highlighted http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70297-3/fulltext.  For years clinicians have remained concerned that we are overusing anti-resorptive agents in advanced breast cancer with bone metastases. This data showed no detriment in outcome with a reduction in the use of zoledronic acid (ZA) to 12 weekly in year 2 of treatment. At the least, this new approach will improve patient convenience , and may impact somewhat on the incidence of  osteonecrosis of the jaw (BONJ).

It is speculative as to how to apply this new data to  denosumab, which  was not assessed in this study. Nevertheless, it is intriguing and not unreasonable to think that a similar result would be seen with denosumab, particularly as it is slightly more effective than ZA in the first instance.

one of the  highlights was the debate between Robert Coleman (Sheffield UK) who has led this area and Gabriel Hortobagyi (MD Anderson, Tx,US). Robert reiterated data presented at SABCS 2013 , a metaanalysis of 36 studies and > 18000 patients showing an  reduction in the development of bone metastases and a 3% improvement in overall mortality for post menopausal women with ER+ve breast cancers.

Hortobagyi’s concerns were statistical, but relevant. There was tremendous heterogeneity amongst the studies, none of the studies met their individual primary endpoint (let alone the metaanalysis), the study outcome  was inversely proportional to size, and there was no interaction between schedule type of agent.

Certainly on the basis of no real data Coleman was recommending a 6 monthly schedule of zoledronic acid as per the Austrian study 12 and also the later part of the schedule of ZA in Coleman’s own AZURE study.

(SW) This is contentious and no bisphosphonate is TGA approved for this indication, nor funded on the PBS. Its use would  need to be case by case and i think logically, related to the absolute  risk of relapse of the individual patient. The toxicities of osteonecrosis of the jaw (albeit low 1-2%) need to be considered also.

it seems clear through multiple studies that carboplatin improves the pCR (pathological complete response rate) in women having NAC (neoadjuvant or preoperative chemotherapy) in the setting of triple negative breast cancer.

It clearly adds toxicity through low white cells, and it remains unclear whether the benefit increases the chance of cure. The jury is still out but certainly could be considered in circumstances where the cancer is not initally responding well to standard therapy.

evidence from San Antonio Breast  Cancer Symposium supporting a small but real advantage for bisphosphonates in  improving outcome for post menopausal women with hormone-driven breast cancer. This probably is through reduction in the development of bone metastases.

It is unclear whether potent intermittent intravenous zoledronic acid is to be preferred over potentially weaker oral agents commonly used in osteoporosis such as risedronate and alendronate.

BCNA will be hosting a community forum for women, their family members and friends in Melbourne on 5 December 2013. We hope you can promote this free event to women in your care through your regular communications or by printing and displaying the promotional poster<http://cl.exct.net/?qs=2423273aea03ec5a05f7e77c79b6f20eee9c199569bb553f246d30cd6a6d1929>. Health professionals are also welcome to attend.

The forum features presentations by breast cancer clinicians on clinical and psychosocial topics, including:

*   Dr Richard de Boer on the latest in treatment and care

*   Jane Fletcher on ways to improve emotional and physical wellbeing

*   Raelene Boyle, Olympian and breast cancer survivor.

Women, partners, family members and friends will benefit from meeting others living with breast cancer and hearing about local breast cancer services and supports available.

Forum details:

Living well beyond breast cancer

Thursday 5 December, 10.00 am – 3.00 pm

Lunch: Refreshments and a light lunch will be served.

Venue: The Event Centre at Flemington Racecourse, Skyline Room (Level 3), 448 Epsom Rd, Flemington, Vic.

Cost: This event is free. Participants are welcome to bring along a partner, family member or friend.

Registration: Register online at www.bcna.org.au/events/forums<http://cl.exct.net/?qs=2423273aea03ec5ae214d904aa486b7caff67615c171c163eac44d5021280f63> or phone 1800 500 258.