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Breast Cancer in Very Young Women Asst. Prof Lazar Popovic, MD, PhD Oncology Institute of Vojvodina University of Novi Sad
Breast Cancer in Very
Young Women
Asst. Prof Lazar Popovic, MD, PhD
Oncology Institute of Vojvodina
University of Novi Sad
“Young age by itself should not be the
reason to prescribe more aggressive
therapy than general recommendations.”
Partridge Breast 2014
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Screening
• Prognosis
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Epidemiology
Hankey JNCI 1994
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Biology and Genetics
Keegan Breast Cancer Res 2012
BC Subtypes by age (ICH) <=40
11%
29%
9%13%
38%Luminal A
Luminal B
Luminal-Her2
Her2
TNBC
>50
20%
31%
15%
8%
26%
Luminal A
Luminal B
Luminal-Her2
Her2
TNBC
<35
10%
47%17%
7%
19%
Luminal A
Luminal B
Luminal-Her2
Her2
TNBC
35-50
25%
52%
11%
5%7%
Luminal A
Luminal B
Luminal-Her2
Her2
TNBC
LA: ER+ PR+/- HER2- Ki67<=14; LB ER+ PR+/- HER2- Ki67>14 L
Her2 ER+ PR+/- HER2+ Her2 ER- PR- HER2+ TNBC ER- PR- HER2-
Morrison Br J Cancer 2012
Cancello Ann Oncol 2012
BC Subtypes by age (GEP)
BC Subtypes (Niš/NS)
0 10 20 30 40 50 60
HR+/HER2-
HR+/HER2+
HR-/HER2+
TNBC
Cvetanovic 2015 (Unpublished Data) Age >=35, n=142
BC Subtypes (Niš/NS)
0 10 20 30 40 50 60
HR+/HER2-
HR+/HER2+
HR-/HER2+
TNBC
Cvetanovic 2015 (Unpublished Data)
64%HR+
32%HER2+
Age >=35, n=142
Delay of diagnosis and advanced
stage
Cancer Syndromes and BCY
• HOBC (Hereditary Breast and Ovarian
Cancer) (BRCA 1/2)
• LI-Fraumeni (TP53)
• Cowden (PTEN)
• Hereditary Diffuse Gastric Cancer (CDH1)
• Peutz-Jeghers (STK11)
Arnold BCY1 2012
HBOC (Hereditary Breast and
Ovarian Cancer)
• BRCA 1/2 mutations in 2-4%, >10% in BC <35 years
• BRCA 1 50-85% risk of BC (Young age!)
• 40-60% risk of second primary BC
• 35-45% risk of ovarian cancer
• Risk for prostate cancer, Hodgkin’s Lymphoma etc.
Arnold BCY1 2012
Why to test for BRCA 1/2
mutations?
• Guide decisions about systemic therapy
(Platinum, PARP inhibitors)
• Guide decisions about screening and
follow up approaches
• Guide decisions about (preventive)
surgery (risk of contralateral BC)
• Define potential risk to family members
Arnold BCY1 2012
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Survival of BC by Age
Azim Clin Cancer Res 2012
Survival of BC by Age
Cancaello Ann Oncol 2010; Anders JCO 2008
Does patients aged <=30 have
worse outcome? DFS
0 20 40 60 80 100 120 140
100
80
60
40
20
0
Months
Su
rviv
al
pro
bab
ilit
y (
%)
Age
<=30
31-35
OS
0 20 40 60 80 100 120 140
100
90
80
70
60
50
40
30
20
10
0
Months
Su
rviv
al p
rob
ab
ilit
y (
%)
Age
<=30
31-35
<=30: n=33 med=32 3y DFS 45.7%
31-35: n=96 med=NR 3y DFS 73.4%
p=0.004 HR=2.60 (CI 1.34-5.09)
<=30: n=34 med=NR 3y OS 70.7%
31-35: n=99 med=NR 3y OS 91.5%
p=0.037 HR=2.33 (CI 1.04-5.18)
Cvetanovic 2015 (Unpublished Data)
Survival of BC by Age and
Subtype
Azim Clin Cancer Res 2012
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Screening in very young
population?
• Only for those with HIGH RISK (20-25%
lifetime risk):
- BRCA carriers, LI-Fraumeni, Cowden,
Fanconi Anemia
- 1st degree relative with BC not tested for
BRCA mut
- Previously Chest Irradiation (Hodgkin’s
Lymphoma)
Mammography
Sklair-Levy BCY2 2014
Mammography
Sklair-Levy BCY2 2014
Sensitivity:85-90% Sensitivity: 50-65%
MRI
...but sometime too sensitive...
Sklair-Levy BCY2 2014
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Surgery
Surgery
T stage Number of patients % Mastectomy
T1 41 31.7%
T2 73 63%
T3 10 80%
Fredholm Plos One 2009
Cvetanovic 2015 (Unpublished Data)
Surgery
Surgery
“Surgical treatment of young patients with EBC-
while being tailored to the individual patient-
should in general not differe from that of older
patients.”
Partridge Breast 2014
“Immediate breast reconstruction after
mastectomy does not seem to affect
survival as compared to mastectomy
without reconstruction...”
Partridge Breast 2014
Hormonal therapy
Pagani NEJM 2014, Prudence NEJM 2014
SOFT & TEXT
HR 0.83
p=0.1
Prudence NEJM 2014
SOFT & TEXT
Prudence NEJM 2014
Neoadjuvant chemotherapy
“something for advanced stages”
Preferred standard in TNBC and Her2+
BC
Loibl BCY2 2014
pCR rates after neoadjuvant
chemo
Loibl Cancer Res 2011
pCR rates after neoadjuvant
chemo
Loibl Cancer Res 2011
44% of all TNBC in women under
35 are BRCA mutated!
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Pregnancy after Breast Cancer
Positive Trial
Breast Cancer in Young Women
• Epidemiology
• Biology and Genetics
• Prognosis
• Screening
• Treatment
• Fertility, Contraception and Premature Menopause
• Pregnancy after Breast Cancer
• QOL issues
• Survivorship
Ferilit
Dr vs. Patient Perspective
Diagnostic tools Surveillance
Heredity High risk for family
Loco-regional treatment Surgery
Cancer biology Cure
Systemic treatment Tailored chemo
Fertility and pregnancy F and P and menopause
Advanced disease Fear of reccurence
QOL QOL, frinedship, sexual life
Survivorship Service provision
Mothering
Social support
Conclusion
• BC in very young women is often agressive disease with poor prognosis
• Young age by itself should not be the reason to prescribe more aggressive therapy than general recommendations
• Pregnancy seems to be safe after BC
• Importance of social and MDs support
• We need new diagnostic tools and new therapies to have better outcomes
Borislav Mandic
“Project 365”
