Should triple negative breast cancer (tnbc) subtype

SHOULD TRIPLE-NEGATIVE
BREAST CANCER (TNBC)
SUBTYPE AFFECT LOCAL-
REGIONAL THERAPY DECISION
MAKING?

What is Triple Negative
Breast cancer?
ER , PR negative
HER 2 neu negative
Aggressive pathologic
features a higher
histology grade and
mitotic index
No hormonal
treatment
NO
Trastuzumab
Higher rate of
&early recurrence
distant metastasis
to brain and lungs

Is There Hope ???!!!!!!!!!!!!!!
Understanding the biology
Basal-like 1 (BL-1) Basal-like 2 (BL-2)
Immunomodulatory (IM) Mesenchymal (M)
Mesenchymal stem-like (MSL) Luminal androgen receptor (LAR)
Triple Negative Breast
Cancer
EGFR & CK5/6 (Positive)
EGFR & CK5/6 (Negative)

Female patient 32 ys old , presented with mass in left breast
(2*3) cm , tru cut biopsy was taken revealed , infiltrating
duct carcinoma , ER , PR ,HER2 neu negative
( Triple Negative) . The patient has come to your office to
discuss her treatment options , she talked to you about her
chance for breast conserving surgery .
What will be your advice?????????
*In order to determine whether surgical choice has an impact
on locoregional recurrence in patients with TNBC, several
studies have investigated outcomes following treatments in
TNBC compared with the general breast cancer population.
*The aggressive nature of the TNBC subtype may appear to
exclude such patients from treatment with breast-conservation
therapy (BCT)

Parker et al* addressed this by carrying out a retrospective analysis of
patients with TNBC, comparing their outcomes based on the surgical
approach (BCT versus mastectomy).
In this study, out of a total of 220 patients with TNBC, 61 (30%) patients
underwent BCT and 141 (70%) patients underwent mastectomy. To
determine whether the type of operative therapy had an impact on the
outcome for patients with TNBC, overall survival (OS) and disease-free
survival (DFS) were compared.
The 5-year DFS rates for the BCT and mastectomy groups
were 68% and 57%, respectively (P = 0.14).
The 5-year OS was better for the BCT than for the
mastectomy group (89% versus 69%; P = 0.018).
Parker et al. concluded that selected
patients with TNBC should be given the
opportunity to benefit from the less
aggressive BCT.
*Parker CC, Ampil F, Burton G et al. Is breast conservation therapy a viable option
for patients with triple-receptor negative breast cancer? Surgery 2010; 148.

Solin et al.* conducted a study of 519 women with breast
cancer, 90 with TNBC. After BCT with radiation, women with
TNBC showed a higher 8-year rate of any locoregional
recurrence (8% versus 4%; P = 0.041) and a lower 8-year
rate of freedom from distant metastases (81% versus 92%; P
= 0.0066).
Although women with TNBC had a higher rate of
locoregional recurrence after breast reconstruction with
RT, Following multivariate analysis, this difference was
not statistically significant.
*Solin LJ, Hwang WT, Vapiwala N. Outcome after breast conservation treatment with radiation for women with triple-
negative early-stage invasive breast carcinoma. Clin Breast Cancer 2009; 9: 96–100.

Voduc et al classified patients into six subtypes, which included
distinction of basal-like (ER/PR/HER2 negative, EFGR positive or CK5/6
positive) and TNBC-phenotype (ER/PR/HER2 negative, EGFR negative
and CK5/6 negative) for analysis of LRR outcomes.
LRR was highest among basal-like, but not nonbasal TNBC, and these
LRR patterns were also similarly high when the two subtypes
underwent BCT. These findings have also been*confirmed in recent
meta-analyses
Abdulkarim et al analyzed LRR outcomes of T1–2, N0 TNBC treated
with BCT compared with modified radical mastectomy and reported an
absolute reduction of LRR risk by 6% in their BCT cohort.**
**Abdulkarim BS, Cuartero J, Hanson J, et al. Increased risk of locoregional recurrence for women with T1-2N0 triple-
negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with
breast-conserving therapy. J Clin Oncol. 2011;29:2852-2858.
*Wang J, Xie X, Wang X, et al. Locoregional and distant recurrences after breast conserving
therapy in patients with triple-negative breast cancer: a meta-analysis. Surg Oncol.
2013;22:247-255

So, your patient has gone for breast conserving surgery with
lumpectomy with negative margin and adequate axillary evacuation
with pathological staging (pT2N0M0) then she has returned to you
for further management .
Here is the question , Does being triple negative will impact your
descion about her adjuvant radiotherapy????
*Adjuvant radiotherapy is a key component in BCS
*Given the ongoing excitement generated by newer radiation delivery methods
that deliver shorter courses of radiation for early-stage breast cancer.
*APBI delivers radiation to a small area surrounding the lumpectomy
cavity (and not all breast tissue) using a variety of delivery methods, reducing
treatment from five to six and a half weeks with conventionally fractionated whole-
breast radiation to less than five days with APBI, thus, lower treatment costs,
increasing patient convenience, and potentially decreasing toxicity with smaller
radiated volumes.
BUT, patterns of recurrence after BCT by subtype suggest
more true recurrences
(around the tumor bed) for TNBC

Although there is a paucity of data on outcomes by subtype from
prospective APBI trials, one recent prospective APBI study found
an unacceptably high five-year actuarial in-breast failure rate of
33% in their TNBC subset *
*Sioshansi S, Ehdaivand S, Cramer C, et al. Triple negative breast cancer is associated with an increased risk of residual
invasive carcinoma after lumpectomy. Cancer. 2012;118:3893-3898

The rising question here , if this patient
had done MRM , is there will be an
indication for adjuvant radiotherapy???
Abdulkarim et al. compared the locoregional recurrence
risk following MRM without adjuvant RT with BCS in a
population of patients with TNBC and a subgroup of patients
with T1-2N0 TNBC.
At a median follow-up of 7.2 years,
%10 of patients with TNBC developed locoregional recurrence,
and MRM without RT represented the only independent
prognostic factor associated with increased risk of locoregional
recurrence in the T1-2N0 subgroup when compared with BCS
Other studies have also suggested that some T1-2N0 patients may
benefit from MRM plus adjuvant RT , which is not recommended in
the current guidelines.

There is a study found a decreased effect of PMRT for patients
with TNBC when compared with other breast cancer subtypes (ER-
positive/PR-positive and the ER-positive/PR-positive/HER2-
negative subtype).
Taken together, the authors suggested relative radioresistance of
the TNBC subtype as a consequence of the ER-negative receptor
status. ER expression results in a decrease in cell-cycle duration,
reducing the time available for the repair of DNA damage caused by
radiation.
It was suggested that ER-negative cells as found in TNBC and
basal-like breast cancer would thus exhibit radioresistance, as DNA
repair is allowed to progress during the slower cell cycle.

Do you think that genetic testing for this patient
will make a sense in decision making for
locoregional management??
*There is some notable overlap between the morphologic and
phenotypic features of breast cancer in BRCA1 carriers and
sporadic TNBC. These strong resemblances suggest a
commonality in one or more defects in the functions of the
BRCA1 pathway for both BRCA1-associated and sporadic
TNBC.
*Although much remains to be learned about the clinical
implications regarding the resemblances between BRCA1-
associated and sporadic TNBC, knowledge of germline BRCA
mutation status is an important component of local-regional
management decisions.

It is essential to recognize that the increased lifetime risk of
ipsilateral breast relapse and contralateral breast cancer after
BCT in BRCA carriers is not shared by sporadic TNBC.
Thus, all patients with TNBC should
undergo risk assessment for genetic
susceptibility
*Though mutation status alone should not direct local-regional
management, it guides recommendations for additional risk-reducing
surgical interventions, such as oophorectomy or contralateral
prophylactic mastectomy, which may be performed simultaneously
with definitive surgery.
*The presence of a BRCA mutation should not preclude BCT in
patients who are otherwise appropriate candidates, as the data
suggest that BC-specific survival and overall survival for hereditary
breast cancer is independent of local treatment choice.

Given the high long-term risks of
new in-breast and contralateral
breast primaries, definitive
mastectomy with simultaneous
contralateral prophylactic
mastectomy is the local-regional
management pathway that is
most commonly selected by
patients with hereditary breast
cancer

Triple negative breast cancer represent a
major obstacle regarding its
aggressiveness and lack of targets to be
targated .
TNBC is not contraindication for
breast conserving surgery.
Following breast conservation ,
conventional radiotherapy with boost is
recommended
Genetic risk assessment for
TNBC is recommended

Searching for targets
is the most important
rising hope in
management of triple
negative breast cancer

Should triple negative breast cancer (tnbc) subtype

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